10-95823354-A-C

Position:

• chr10-95823354-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001776.6(ENTPD1):​c.134A>C​(p.Glu45Ala) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENTPD1 NM_001776.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.52

Genes affected

ENTPD1 (HGNC:3363): (ectonucleoside triphosphate diphosphohydrolase 1) The protein encoded by this gene is a plasma membrane protein that hydrolyzes extracellular ATP and ADP to AMP. Inhibition of this protein's activity may confer anticancer benefits. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

ENTPD1-AS1 (HGNC:45203): (ENTPD1 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14225104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENTPD1	NM_001776.6	c.134A>C	p.Glu45Ala	missense_variant	2/10	ENST00000371205.5	NP_001767.3
ENTPD1-AS1	NR_038444.1	n.533+24038T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENTPD1	ENST00000371205.5	c.134A>C	p.Glu45Ala	missense_variant	2/10	1	NM_001776.6	ENSP00000360248	P1
ENTPD1-AS1	ENST00000669711.1	n.444-38109T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2023

The c.170A>C (p.E57A) alteration is located in exon 2 (coding exon 2) of the ENTPD1 gene. This alteration results from a A to C substitution at nucleotide position 170, causing the glutamic acid (E) at amino acid position 57 to be replaced by an alanine (A). 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	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.11	.;.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.032
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	.;.;L
MutationTaster	Benign	0.63	D;D;D;D;D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.059
Sift	Benign	0.66	T;T;T
Sift4G	Benign	0.69	T;T;T
Polyphen		0.0030	B;.;P
Vest4		0.31
MutPred		0.41		.;.;Loss of methylation at K48 (P = 0.0686);
MVP		0.18
MPC		0.37
ClinPred		0.49	T
GERP RS		4.1
Varity_R		0.11
gMVP		0.36

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: chr10-97583111;