U.S. flag

An official website of the United States government

NM_003680.4(YARS1):c.1276del (p.Asn425_Leu426insTer) AND Charcot-Marie-Tooth disease dominant intermediate C

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 19, 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:
RCV001350368.3

Allele description

NM_003680.4(YARS1):c.1276del (p.Asn425_Leu426insTer)

Gene:
YARS1:tyrosyl-tRNA synthetase 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
1p35.1
Genomic location:
Preferred name:
NM_003680.4(YARS1):c.1276del (p.Asn425_Leu426insTer)
HGVS:
  • NC_000001.11:g.32780144del
  • NG_008408.1:g.42890del
  • NM_003680.3:c.1276delC
  • NM_003680.4:c.1276delMANE SELECT
  • NP_003671.1:p.Asn425_Leu426insTer
  • LRG_273t1:c.1276del
  • LRG_273:g.42890del
  • NC_000001.10:g.33245744del
  • NC_000001.10:g.33245745del
Links:
dbSNP: rs764028295
NCBI 1000 Genomes Browser:
rs764028295
Molecular consequence:
  • NM_003680.4:c.1276del - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Charcot-Marie-Tooth disease dominant intermediate C (CMTDIC)
Synonyms:
CHARCOT-MARIE-TOOTH NEUROPATHY, DOMINANT INTERMEDIATE C
Identifiers:
MONDO: MONDO:0012012; MedGen: C1842237; OMIM: 608323

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001544761Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Mar 19, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 Invitae, SCV001544761.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 1045888). This variant has not been reported in the literature in individuals affected with YARS-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu426*) in the YARS gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in YARS cause disease.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 7, 2024