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NM_000057.4(BLM):c.3044C>T (p.Thr1015Ile) AND not provided

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Nov 3, 2021
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000115302.5

Allele description [Variation Report for NM_000057.4(BLM):c.3044C>T (p.Thr1015Ile)]

NM_000057.4(BLM):c.3044C>T (p.Thr1015Ile)

Gene:
BLM:BLM RecQ like helicase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q26.1
Genomic location:
Preferred name:
NM_000057.4(BLM):c.3044C>T (p.Thr1015Ile)
Other names:
p.T1015I:ACA>ATA
HGVS:
  • NC_000015.10:g.90794191C>T
  • NG_007272.1:g.81820C>T
  • NM_000057.4:c.3044C>TMANE SELECT
  • NM_001287246.2:c.3044C>T
  • NM_001287247.2:c.3044C>T
  • NM_001287248.2:c.1919C>T
  • NP_000048.1:p.Thr1015Ile
  • NP_001274175.1:p.Thr1015Ile
  • NP_001274176.1:p.Thr1015Ile
  • NP_001274177.1:p.Thr640Ile
  • LRG_20t1:c.3044C>T
  • LRG_20:g.81820C>T
  • NC_000015.9:g.91337421C>T
  • NM_000057.2:c.3044C>T
  • NM_000057.3:c.3044C>T
Protein change:
T1015I
Links:
dbSNP: rs202196488
NCBI 1000 Genomes Browser:
rs202196488
Molecular consequence:
  • NM_000057.4:c.3044C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287246.2:c.3044C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287247.2:c.3044C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287248.2:c.1919C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000149211GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Uncertain significance
(Jan 27, 2014) 		germlineclinical testing

Citation Link,

SCV002010756Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Nov 3, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot 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 GeneDx, SCV000149211.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Single pathogenic variants in BLM have only recently been described in association with cancer predisposition and the risks are not well understood. This variant is denoted BLM c.3044C>T at the cDNA level, p.Thr1015Ile (T1015I) at the protein level, and results in the change of a Threonine to an Isoleucine (ACA>ATA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BLM Thr1015Ile was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative substitution of a neutral polar amino acid for a neutral non-polar one, altering a position that is well conserved throughout evolution and is located in the Helicase C-terminal domain per UNIPROT and Interpro. Multiple in silico algorithms predict that this variant may be damaging to protein structure and function. On a molecular level, the impact of this missense variant on protein structure and function is not known and thus we consider this to be a variant of uncertain significance. Furthermore, based on the currently available information, cancer risks associated with this variant, and with single variants in BLM in general, remain unclear.

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

From Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden, SCV002010756.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 7, 2024