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NM_001033855.3(DCLRE1C):c.47T>C (p.Ile16Thr) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 11, 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:
RCV003323874.2

Allele description [Variation Report for NM_001033855.3(DCLRE1C):c.47T>C (p.Ile16Thr)]

NM_001033855.3(DCLRE1C):c.47T>C (p.Ile16Thr)

Gene:
DCLRE1C:DNA cross-link repair 1C [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10p13
Genomic location:
Preferred name:
NM_001033855.3(DCLRE1C):c.47T>C (p.Ile16Thr)
Other names:
NM_001033855.3(DCLRE1C):c.47T>C; p.Ile16Thr
HGVS:
  • NC_000010.11:g.14953964A>G
  • NG_007276.1:g.5132T>C
  • NM_001033855.2:c.47T>C
  • NM_001033855.3:c.47T>CMANE SELECT
  • NM_001033857.3:c.-399T>C
  • NM_001033858.3:c.-721T>C
  • NM_001289076.2:c.-158T>C
  • NM_001289077.2:c.-445T>C
  • NM_001289078.2:c.-191T>C
  • NM_001289079.2:c.-767T>C
  • NM_001350965.2:c.47T>C
  • NM_001350966.2:c.-191T>C
  • NM_001350967.2:c.-399T>C
  • NM_022487.4:c.-243T>C
  • NP_001029027.1:p.Ile16Thr
  • NP_001337894.1:p.Ile16Thr
  • LRG_54:g.5132T>C
  • NC_000010.10:g.14995963A>G
  • NM_001033855.3:c.47T>C
  • NR_110297.2:n.133T>C
  • NR_146960.1:n.469T>C
  • NR_146961.2:n.133T>C
  • NR_146962.1:n.469T>C
Protein change:
I16T
Links:
dbSNP: rs1317003987
NCBI 1000 Genomes Browser:
rs1317003987
Molecular consequence:
  • NM_001033857.3:c.-399T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001033858.3:c.-721T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001289076.2:c.-158T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001289077.2:c.-445T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001289078.2:c.-191T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001289079.2:c.-767T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001350966.2:c.-191T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001350967.2:c.-399T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_022487.4:c.-243T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001033855.3:c.47T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350965.2:c.47T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_110297.2:n.133T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146960.1:n.469T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146961.2:n.133T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146962.1:n.469T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004028835Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Jul 11, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Damaging-agent sensitivity of Artemis-deficient cell lines.

Musio A, Marrella V, Sobacchi C, Rucci F, Fariselli L, Giliani S, Lanzi G, Notarangelo LD, Delia D, Colombo R, Vezzoni P, Villa A.

Eur J Immunol. 2005 Apr;35(4):1250-6.

PubMed [citation]
PMID:
15770702

Functional analysis of naturally occurring DCLRE1C mutations and correlation with the clinical phenotype of ARTEMIS deficiency.

Felgentreff K, Lee YN, Frugoni F, Du L, van der Burg M, Giliani S, Tezcan I, Reisli I, Mejstrikova E, de Villartay JP, Sleckman BP, Manis J, Notarangelo LD.

J Allergy Clin Immunol. 2015 Jul;136(1):140-150.e7. doi: 10.1016/j.jaci.2015.03.005. Epub 2015 Apr 25.

PubMed [citation]
PMID:
25917813
PMCID:
PMC4494888
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004028835.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: DCLRE1C c.47T>C (p.Ile16Thr) results in a non-conservative amino acid change located in the metallo-beta-lactamase domain (Musio_2005, Felgentreff_2015) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251244 control chromosomes (gnomAD v2.1, Exomes dataset). c.47T>C has been reported in the literature in at least two compound heterozygous individuals affected with Severe Combined Immunodeficiency (e.g., Musio_2005, Felgentreff_2015, Cowan_2022). These data indicate that the variant may be associated with disease. At least two publications report experimental evidence evaluating an impact on protein function, finding that the variant results in an approximately 20% reduction in recombination activity and DNA repair activity relative to wild-type in vitro (e.g., Musio_2005, Felgentreff_2015). The following publications have been ascertained in the context of this evaluation (PMID: 25917813, 15770702, 36546626). One submitter has reported clinical-significance assessments for this variant to ClinVar after 2014, citing overlapping evidence, and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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

Last Updated: Apr 7, 2025