NM_001032382.2(PQBP1):c.778C>T (p.Arg260Ter) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Jun 26, 2023
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000578765.9

Allele description [Variation Report for NM_001032382.2(PQBP1):c.778C>T (p.Arg260Ter)]

NM_001032382.2(PQBP1):c.778C>T (p.Arg260Ter)

Gene:

PQBP1:polyglutamine binding protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp11.23

Genomic location:

Preferred name:

NM_001032382.2(PQBP1):c.778C>T (p.Arg260Ter)

HGVS:

NC_000023.11:g.48903064C>T
NG_015967.1:g.10147C>T
NG_015968.2:g.86G>A
NG_034300.1:g.13895G>A
NM_001032381.2:c.778C>T
NM_001032382.2:c.778C>TMANE SELECT
NM_001032383.2:c.778C>T
NM_001032384.1:c.778C>T
NM_001167989.2:c.775C>T
NM_001167990.2:c.754C>T
NM_001167992.1:c.478C>T
NM_005710.2:c.778C>T
NM_144495.3:c.493C>T
NP_001027553.1:p.Arg260Ter
NP_001027554.1:p.Arg260Ter
NP_001027555.1:p.Arg260Ter
NP_001027556.1:p.Arg260Ter
NP_001161461.1:p.Arg259Ter
NP_001161462.1:p.Arg252Ter
NP_001161464.1:p.Arg160Ter
NP_005701.1:p.Arg260Ter
NP_652766.1:p.Arg165Ter
NC_000023.10:g.48760341C>T

Protein change:

R160*

Links:

dbSNP: rs781987043

NCBI 1000 Genomes Browser:

rs781987043

Molecular consequence:

NM_001032381.2:c.778C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001032382.2:c.778C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001032383.2:c.778C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001032384.1:c.778C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001167989.2:c.775C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001167990.2:c.754C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001167992.1:c.478C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_005710.2:c.778C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_144495.3:c.493C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000681117	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jun 26, 2023)	germline	clinical testing	Citation Link,
SCV001251795	Genomic Research Center, Shahid Beheshti University of Medical Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 3, 2020)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004647942	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 18, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000681117

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jun 26, 2023)

germline

clinical testing

Citation Link,

SCV001251795

Genomic Research Center, Shahid Beheshti University of Medical Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 3, 2020)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004647942

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 18, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From GeneDx, SCV000681117.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Nonsense variant predicted to result in protein truncation as the last 6 amino acids are lost, although loss-of-function variants have not been reported downstream of this position in the protein; Has not been previously published as pathogenic or benign to our knowledge

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genomic Research Center, Shahid Beheshti University of Medical Sciences, SCV001251795.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004647942.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 489131). This variant has not been reported in the literature in individuals affected with PQBP1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Arg260*) in the PQBP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 6 amino acid(s) of the PQBP1 protein.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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