10-113850156-C-T

Variant names:

• chr10-113850156-C-T
• rs3750898
• NM_014881.5:c.949G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014881.5(DCLRE1A):​c.949G>A​(p.Asp317Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DCLRE1A NM_014881.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 33 publications found

Genes affected

DCLRE1A (HGNC:17660): (DNA cross-link repair 1A) This gene encodes a conserved protein that is involved in the repair of DNA interstrand cross-links. DNA cross-links suppress transcription, replication, and DNA segregation. The encoded protein is a regulator of the mitotic cell cycle checkpoint. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

ENSG00000288933 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18470687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLRE1A	NM_014881.5	c.949G>A	p.Asp317Asn	missense_variant	Exon 2 of 9	ENST00000361384.7	NP_055696.3
DCLRE1A	NM_001271816.2	c.949G>A	p.Asp317Asn	missense_variant	Exon 3 of 10		NP_001258745.1
DCLRE1A	XM_006718090.2	c.949G>A	p.Asp317Asn	missense_variant	Exon 3 of 10		XP_006718153.1
DCLRE1A	XM_011540429.2	c.949G>A	p.Asp317Asn	missense_variant	Exon 3 of 10		XP_011538731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLRE1A	ENST00000361384.7	c.949G>A	p.Asp317Asn	missense_variant	Exon 2 of 9	1	NM_014881.5	ENSP00000355185.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 69

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;T
Eigen	Benign	-0.070
Eigen_PC	Benign	-0.049
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.53	.;T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.6	L;L
PhyloP100		1.1
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.53	N;N
REVEL	Benign	0.19
Sift	Uncertain	0.022	D;D
Sift4G	Benign	0.44	T;T
Polyphen		0.65	P;P
Vest4		0.11
MutPred		0.11		Gain of methylation at K315 (P = 0.0718);Gain of methylation at K315 (P = 0.0718);
MVP		0.82
MPC		0.35
ClinPred		0.74	D
GERP RS		4.1
Varity_R		0.083
gMVP		0.11
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs3750898; hg19: chr10-115609915;