rs143042511
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1
The NM_001033855.3(DCLRE1C):āc.762T>Cā(p.His254=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,614,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.00068 ( 0 hom., cov: 32)
Exomes š: 0.000056 ( 0 hom. )
Consequence
DCLRE1C
NM_001033855.3 synonymous
NM_001033855.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.531
Genes affected
DCLRE1C (HGNC:17642): (DNA cross-link repair 1C) This gene encodes a nuclear protein that is involved in V(D)J recombination and DNA repair. The encoded protein has single-strand-specific 5'-3' exonuclease activity; it also exhibits endonuclease activity on 5' and 3' overhangs and hairpins. The protein also functions in the regulation of the cell cycle in response to DNA damage. Mutations in this gene can cause Athabascan-type severe combined immunodeficiency (SCIDA) and Omenn syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 10-14932872-A-G is Benign according to our data. Variant chr10-14932872-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 536372.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.531 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000676 (103/152330) while in subpopulation AFR AF= 0.00245 (102/41582). AF 95% confidence interval is 0.00207. There are 0 homozygotes in gnomad4. There are 40 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DCLRE1C | NM_001033855.3 | c.762T>C | p.His254= | synonymous_variant | 9/14 | ENST00000378278.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DCLRE1C | ENST00000378278.7 | c.762T>C | p.His254= | synonymous_variant | 9/14 | 1 | NM_001033855.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000683 AC: 104AN: 152212Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000135 AC: 34AN: 251478Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135910
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GnomAD4 exome AF: 0.0000561 AC: 82AN: 1461888Hom.: 0 Cov.: 33 AF XY: 0.0000481 AC XY: 35AN XY: 727246
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GnomAD4 genome ? AF: 0.000676 AC: 103AN: 152330Hom.: 0 Cov.: 32 AF XY: 0.000537 AC XY: 40AN XY: 74482
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Severe combined immunodeficiency due to DCLRE1C deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at