10-14945139-G-C

Position:

• chr10-14945139-G-C

Variant summary

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

The NM_001033855.3(DCLRE1C):​c.212C>G​(p.Thr71Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,612,574 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: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000021 (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/exons	MANE	Protein	UniProt
DCLRE1C	NM_001033855.3	c.212C>G	p.Thr71Arg	missense_variant	3/14	ENST00000378278.7	NP_001029027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCLRE1C	ENST00000378278.7	c.212C>G	p.Thr71Arg	missense_variant	3/14	1	NM_001033855.3	ENSP00000367527	P2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151920 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460654 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 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: 0.0000233

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151920 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 74204

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	.;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	0.55	N;N
MutationTaster	Benign	0.91	D;D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.9	N;N
REVEL	Uncertain	0.44
Sift	Uncertain	0.0060	D;T
Sift4G	Benign	0.57	T;T
Polyphen		0.98	D;D
Vest4		0.75
MutPred		0.41		Gain of MoRF binding (P = 0.0207);Gain of MoRF binding (P = 0.0207);
MVP		0.88
MPC		0.16
ClinPred		0.77	D
GERP RS		4.3
Varity_R		0.25
gMVP		0.60

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

LitVar

Other links and lift over

dbSNP: rs147013097; hg19: chr10-14987138;