chr10-99661546-A-G

Position:

• chr10-99661546-A-G

Variant summary

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

The NM_020354.5(ENTPD7):​c.109A>G​(p.Ile37Val) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENTPD7 NM_020354.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.357

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

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=0.084632784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENTPD7	NM_020354.5	c.109A>G	p.Ile37Val	missense_variant	3/13	ENST00000370489.5	NP_065087.1
ENTPD7	NM_001349962.2	c.115A>G	p.Ile39Val	missense_variant	4/14		NP_001336891.1
ENTPD7	NM_001349963.2	c.109A>G	p.Ile37Val	missense_variant	3/13		NP_001336892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENTPD7	ENST00000370489.5	c.109A>G	p.Ile37Val	missense_variant	3/13	1	NM_020354.5	ENSP00000359520.4
ENSG00000285932	ENST00000649102.1	n.*654-7641T>C		intron_variant				ENSP00000497114.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Aug 19, 2024

The c.109A>G (p.I37V) alteration is located in exon 3 (coding exon 2) of the ENTPD7 gene. This alteration results from a A to G substitution at nucleotide position 109, causing the isoleucine (I) at amino acid position 37 to be replaced by a valine (V). 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	0.068
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	10
DANN	Benign	0.71
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.0	L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.033
Sift	Benign	0.95	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.17
MutPred		0.63		Loss of catalytic residue at L42 (P = 0.0447);
MVP		0.12
MPC		0.13
ClinPred		0.053	T
GERP RS		2.0
Varity_R		0.013
gMVP		0.25

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: chr10-101421303;