NM_002109.6(HARS1):c.80G>A (p.Ser27Asn) AND Usher syndrome type 3B

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 10, 2023
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:: RCV002975211.3

Allele description [Variation Report for NM_002109.6(HARS1):c.80G>A (p.Ser27Asn)]

NM_002109.6(HARS1):c.80G>A (p.Ser27Asn)

Genes:

LOC129994848:ATAC-STARR-seq lymphoblastoid active region 23285 [Gene]
HARS1:histidyl-tRNA synthetase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q31.3

Genomic location:

Preferred name:

NM_002109.6(HARS1):c.80G>A (p.Ser27Asn)

HGVS:

NC_000005.10:g.140691225C>T
NG_021415.1:g.4793C>T
NG_032158.1:g.5162G>A
NG_070993.1:g.21C>T
NM_001258040.3:c.80G>A
NM_001258041.3:c.80G>A
NM_001258042.3:c.80G>A
NM_001289092.2:c.80G>A
NM_001289093.2:c.80G>A
NM_001289094.2:c.3+77G>A
NM_002109.6:c.80G>AMANE SELECT
NP_001244969.1:p.Ser27Asn
NP_001244970.1:p.Ser27Asn
NP_001244971.1:p.Ser27Asn
NP_001276021.1:p.Ser27Asn
NP_001276022.1:p.Ser27Asn
NP_002100.2:p.Ser27Asn
LRG_1374t1:c.80G>A
LRG_1374:g.5162G>A
LRG_1374p1:p.Ser27Asn
LRG_1376:g.4793C>T
NC_000005.9:g.140070810C>T

Protein change:

S27N

Molecular consequence:

NM_001289094.2:c.3+77G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001258040.3:c.80G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001258041.3:c.80G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001258042.3:c.80G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001289092.2:c.80G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001289093.2:c.80G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002109.6:c.80G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Usher syndrome type 3B
Synonyms:: USHER SYNDROME, TYPE IIIB
Identifiers:: MONDO: MONDO:0013788; MedGen: C3281066; OMIM: 614504

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003279622	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 10, 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

SCV003279622

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 10, 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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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, SCV003279622.2

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

Description

This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 27 of the HARS protein (p.Ser27Asn). This variant is not present in population databases (gnomAD no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 2068936). This variant has not been reported in the literature in individuals affected with HARS-related conditions.

#	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

ClinVar

Relating variation to medicine