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NM_198253.3(TERT):c.1234C>T (p.His412Tyr) AND multiple conditions

Germline classification:
Likely benign (1 submission)
Last evaluated:
Nov 9, 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:
RCV003224095.8

Allele description [Variation Report for NM_198253.3(TERT):c.1234C>T (p.His412Tyr)]

NM_198253.3(TERT):c.1234C>T (p.His412Tyr)

Gene:
TERT:telomerase reverse transcriptase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5p15.33
Genomic location:
Preferred name:
NM_198253.3(TERT):c.1234C>T (p.His412Tyr)
HGVS:
  • NC_000005.10:g.1293652G>A
  • NG_009265.1:g.6396C>T
  • NM_001193376.3:c.1234C>T
  • NM_198253.3:c.1234C>TMANE SELECT
  • NP_001180305.1:p.His412Tyr
  • NP_937983.2:p.His412Tyr
  • NP_937983.2:p.His412Tyr
  • LRG_343t1:c.1234C>T
  • LRG_343:g.6396C>T
  • LRG_343p1:p.His412Tyr
  • NC_000005.9:g.1293767G>A
  • NM_198253.2:c.1234C>T
  • NR_149162.3:n.1313C>T
  • NR_149163.3:n.1313C>T
  • O14746:p.His412Tyr
Protein change:
H412Y; HIS412TYR
Links:
UniProtKB: O14746#VAR_025149; OMIM: 187270.0002; dbSNP: rs34094720
NCBI 1000 Genomes Browser:
rs34094720
Molecular consequence:
  • NM_001193376.3:c.1234C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198253.3:c.1234C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_149162.3:n.1313C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_149163.3:n.1313C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Acute myeloid leukemia (AML)
Synonyms:
Acute myeloid leukemia, adult; AML adult; Acute myelogenous leukemia; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0018874; MeSH: D015470; MedGen: C0023467; Orphanet: 519; OMIM: 601626; Human Phenotype Ontology: HP:0004808
Name:
Dyskeratosis congenita, autosomal dominant 2
Identifiers:
MONDO: MONDO:0013521; MedGen: C3151443; OMIM: 613989
Name:
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1
Synonyms:
PULMONARY FIBROSIS AND/OR BONE MARROW FAILURE SYNDROME, TELOMERE-RELATED, 1
Identifiers:
MONDO: MONDO:0013878; MedGen: C3553617; Orphanet: 88; OMIM: 614742
Name:
Melanoma, cutaneous malignant, susceptibility to, 9
Synonyms:
Cutaneous malignant melanoma 9
Identifiers:
MONDO: MONDO:0014056; MedGen: C3554574; Orphanet: 618; OMIM: 615134

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003920547Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely benign
(Nov 9, 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

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

Details of each submission

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV003920547.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This variant has been reported in the literature in at least 6 individuals with varying phenotypes (aplastic anemia, idiopathic interstitial pneumonias, hypoxemia, diffuse cutaneous systemic sclerosis, and bone marrow failure) (Yamaguchi 2005 PMID:15814878, Alder 2008 PMID:18753630, Sugino 2015 PMID:26576048, Mak 2016 PMID:27111861, Bluteau 2018 PMID:29146883). However, this variant is present in 0.4% (384/83108) of European alleles, including 2 homozygotes, in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/5-1293767-G-A?dataset=gnomad_r2_1). This variant is present in ClinVar, with several labs classifying this variant as likely benign or benign (Variation ID:12730). Evolutionary conservation suggests that this variant may not impact the protein; computational predictive tools for this variant are unclear. Functional studies for this variant have reported a wide range of outcomes from a reduction in activity to 36% of wild-type to near normal activity (Yamaguchi 2005 PMID:15814878, Alder 2008 PMID:18753630, Du 2008 PMID:18042801, Zaug 2013 PMID:23901009). In summary, data on this variant suggests that this variant does not cause disease, but requires further evidence. Therefore, this variant is classified as Likely Benign.

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

Last Updated: May 1, 2024