10-113841488-A-G

Position:

• chr10-113841488-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014881.5(DCLRE1A):​c.2738T>C​(p.Ile913Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DCLRE1A NM_014881.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.60

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35703608).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCLRE1A	NM_014881.5	c.2738T>C	p.Ile913Thr	missense_variant	7/9	ENST00000361384.7	NP_055696.3
DCLRE1A	NM_001271816.2	c.2738T>C	p.Ile913Thr	missense_variant	8/10		NP_001258745.1
DCLRE1A	XM_006718090.2	c.2738T>C	p.Ile913Thr	missense_variant	8/10		XP_006718153.1
DCLRE1A	XM_011540429.2	c.2738T>C	p.Ile913Thr	missense_variant	8/10		XP_011538731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCLRE1A	ENST00000361384.7	c.2738T>C	p.Ile913Thr	missense_variant	7/9	1	NM_014881.5	ENSP00000355185.2
DCLRE1A	ENST00000369305.1	c.2738T>C	p.Ile913Thr	missense_variant	8/10	5		ENSP00000358311.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461366 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727006

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: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 09, 2024

The c.2738T>C (p.I913T) alteration is located in exon 7 (coding exon 7) of the DCLRE1A gene. This alteration results from a T to C substitution at nucleotide position 2738, causing the isoleucine (I) at amino acid position 913 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.0034	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Benign	0.52
DEOGEN2	Benign	0.069	T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.58	.;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.040	N;N
REVEL	Benign	0.17
Sift	Benign	0.31	T;T
Sift4G	Benign	0.62	T;T
Polyphen		0.075	B;B
Vest4		0.59
MutPred		0.57		Loss of stability (P = 0.0423);Loss of stability (P = 0.0423);
MVP		0.72
MPC		0.16
ClinPred		0.65	D
GERP RS		2.7
Varity_R		0.12
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-115601247;