10-14945139-G-T

Variant names:

• chr10-14945139-G-T
• NM_001033855.3:c.212C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001033855.3(DCLRE1C):​c.212C>A​(p.Thr71Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,654 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DCLRE1C NM_001033855.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLRE1C	NM_001033855.3	c.212C>A	p.Thr71Lys	missense_variant	Exon 3 of 14	ENST00000378278.7	NP_001029027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLRE1C	ENST00000378278.7	c.212C>A	p.Thr71Lys	missense_variant	Exon 3 of 14	1	NM_001033855.3	ENSP00000367527.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460654 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726540

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.25	.;T
Eigen	Benign	-0.016
Eigen_PC	Benign	0.094
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.6	N;N
REVEL	Uncertain	0.32
Sift	Benign	0.099	T;T
Sift4G	Benign	0.93	T;T
Polyphen		0.54	P;B
Vest4		0.71
MutPred		0.44		Gain of MoRF binding (P = 0.0404);Gain of MoRF binding (P = 0.0404);
MVP		0.83
MPC		0.11
ClinPred		0.69	D
GERP RS		4.3
Varity_R		0.21
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-14987138;