NM_177939.3(P4HTM):c.184del (p.Leu62fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 5, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003063289.2

Allele description [Variation Report for NM_177939.3(P4HTM):c.184del (p.Leu62fs)]

NM_177939.3(P4HTM):c.184del (p.Leu62fs)

Genes:

LOC129936725:ATAC-STARR-seq lymphoblastoid silent region 14344 [Gene]
P4HTM:prolyl 4-hydroxylase, transmembrane [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3p21.31

Genomic location:

Preferred name:

NM_177939.3(P4HTM):c.184del (p.Leu62fs)

HGVS:

NC_000003.12:g.48990440del
NM_177938.2:c.184del
NM_177939.3:c.184delMANE SELECT
NP_808807.2:p.Leu62fs
NP_808808.1:p.Leu62fs
NC_000003.11:g.49027872del
NC_000003.11:g.49027873del

Protein change:

L62fs

Molecular consequence:

NM_177938.2:c.184del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_177939.3:c.184del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV003455019	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 5, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30940925, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003455019

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 5, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Biallelic loss-of-function P4HTM gene variants cause hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy, and eye abnormalities (HIDEA syndrome).

Rahikkala E, Myllykoski M, Hinttala R, Vieira P, Nayebzadeh N, Weiss S, Plomp AS, Bittner RE, Kurki MI, Kuismin O, Lewis AM, Väisänen ML, Kokkonen H, Westermann J, Bernert G, Tuominen H, Palotie A, Aaltonen L, Yang Y, Potocki L, Moilanen J, van Koningsbruggen S, et al.

Genet Med. 2019 Oct;21(10):2355-2363. doi: 10.1038/s41436-019-0503-4. Epub 2019 Apr 3.

PubMed [citation]

PMID:: 30940925
PMCID:: PMC6774999

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003455019.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Leu62Trpfs*3) in the P4HTM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in P4HTM are known to be pathogenic (PMID: 30940925). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with P4HTM-related conditions. For these reasons, this variant has been classified as Pathogenic.

#	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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