10-95866183-G-T

Variant names:

• chr10-95866183-G-T
• rs145994698
• NM_001776.6:c.1333G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001776.6(ENTPD1):​c.1333G>T​(p.Gly445Cys) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G445R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENTPD1 NM_001776.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.953
• Publications: 0 publications found

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]

ENSG00000270099 (HGNC:):

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36631793).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001776.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD1	NM_001776.6	MANE Select	c.1333G>T	p.Gly445Cys	missense	Exon 10 of 10	NP_001767.3
	ENTPD1	NM_001440932.1		c.1411G>T	p.Gly471Cys	missense	Exon 10 of 10	NP_001427861.1
	ENTPD1	NM_001164178.1		c.1369G>T	p.Gly457Cys	missense	Exon 10 of 10	NP_001157650.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD1	ENST00000371205.5	TSL:1 MANE Select	c.1333G>T	p.Gly445Cys	missense	Exon 10 of 10	ENSP00000360248.4
	ENTPD1	ENST00000453258.6	TSL:1	c.1354G>T	p.Gly452Cys	missense	Exon 10 of 10	ENSP00000390955.2
	ENTPD1	ENST00000635076.1	TSL:1	n.*908G>T		non_coding_transcript_exon	Exon 8 of 8	ENSP00000489250.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	0.076
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.25	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		0.95
PrimateAI	Benign	0.25	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.094
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.27
MutPred		0.70		Gain of catalytic residue at G445 (P = 0.0477)
MVP		0.29
MPC		0.57
ClinPred		0.88	D
GERP RS		2.0
Varity_R		0.40
gMVP		0.64
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs145994698; hg19: chr10-97625940;