NM_198253.3(TERT):c.1234C>T (p.His412Tyr) AND Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Apr 27, 2017
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:: RCV000013567.36

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:: 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000033814	OMIM	no assertion criteria provided	Pathogenic (Feb 1, 2008)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 15814878, 18042801
SCV000452696	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Likely benign (Apr 27, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000033814

OMIM

no assertion criteria provided

Pathogenic
(Feb 1, 2008)

germline

literature only

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

SCV000452696

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Likely benign
(Apr 27, 2017)

germline

clinical testing

Citation Link

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
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia.

Yamaguchi H, Calado RT, Ly H, Kajigaya S, Baerlocher GM, Chanock SJ, Lansdorp PM, Young NS.

N Engl J Med. 2005 Apr 7;352(14):1413-24.

PubMed [citation]

PMID:: 15814878

Complex inheritance pattern of dyskeratosis congenita in two families with 2 different mutations in the telomerase reverse transcriptase gene.

Du HY, Pumbo E, Manley P, Field JJ, Bayliss SJ, Wilson DB, Mason PJ, Bessler M.

Blood. 2008 Feb 1;111(3):1128-30. Epub 2007 Nov 27.

PubMed [citation]

PMID:: 18042801
PMCID:: PMC2214749

Details of each submission

From OMIM, SCV000033814.3

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

Description

In 2 unrelated patients with telomere-related bone marrow failure (PFBMFT1; 614742), Yamaguchi et al. (2005) identified heterozygosity for a his412-to-tyr missense mutation (H412Y) in exon 2 of the TERT gene. Telomere length in patient granulocytes was less than 10% of control values, and cell lysates carrying the mutation showed about 50% telomerase activity.

In a Scottish man with autosomal recessive dyskeratosis congenita-4 (DKCB4; see 613989), Du et al. (2008) identified compound heterozygosity for H412Y and P704S (187270.0014). Du et al. (2008) showed that the mutant H412Y protein had 36% residual activity.

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

From Illumina Laboratory Services, Illumina, SCV000452696.3

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

#	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: Nov 3, 2024

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