10-99679458-T-C

Variant names:

• chr10-99679458-T-C
• NM_020354.5:c.389T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020354.5(ENTPD7):​c.389T>C​(p.Ile130Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: ENTPD7 NM_020354.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67
• Publications: 0 publications found

Genes affected

ENTPD7 (HGNC:19745): (ectonucleoside triphosphate diphosphohydrolase 7) This gene encodes a purine-converting ectoenzyme which belongs to the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) family. The encoded protein hydrolyzes extracellular nucleoside triphosphates (UTP, GTP, and CTP) to nucleoside monophosphates as part of a purinergic signaling pathway. It contains two transmembrane domains at the N- and C-termini and a large, hydrophobic catalytic domain located in between. This gene affects oxidative stress as well as DNA damage and is a mediator of senescence. [provided by RefSeq, Mar 2017]

ENSG00000285932 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.849

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020354.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD7	NM_020354.5	MANE Select	c.389T>C	p.Ile130Thr	missense	Exon 4 of 13	NP_065087.1	Q9NQZ7
	ENTPD7	NM_001349962.2		c.395T>C	p.Ile132Thr	missense	Exon 5 of 14	NP_001336891.1
	ENTPD7	NM_001349963.2		c.389T>C	p.Ile130Thr	missense	Exon 4 of 13	NP_001336892.1	Q9NQZ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD7	ENST00000370489.5	TSL:1 MANE Select	c.389T>C	p.Ile130Thr	missense	Exon 4 of 13	ENSP00000359520.4	Q9NQZ7
	ENSG00000285932	ENST00000649102.1		n.*576+311A>G		intron	N/A	ENSP00000497114.1	A0A3B3IRX1
	ENTPD7	ENST00000902361.1		c.389T>C	p.Ile130Thr	missense	Exon 3 of 12	ENSP00000572420.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 29

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.081	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		7.7
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.26
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.070	T
Polyphen		0.98	D
Vest4		0.74
MutPred		0.76		Gain of phosphorylation at I130 (P = 0.0147)
MVP		0.39
MPC		0.71
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.55
gMVP		0.76
Mutation Taster		=29/71	disease causing

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

hg19: chr10-101439215;