chr10-99685842-T-A

Variant names:

• chr10-99685842-T-A
• NM_020354.5:c.599T>A

Variant summary

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

The NM_020354.5(ENTPD7):​c.599T>A​(p.Phe200Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 6.8e-7 (0 hom.)
• Consequence: ENTPD7 NM_020354.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.45

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29432678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTPD7	NM_020354.5	c.599T>A	p.Phe200Tyr	missense_variant	Exon 6 of 13	ENST00000370489.5	NP_065087.1
ENTPD7	NM_001349962.2	c.605T>A	p.Phe202Tyr	missense_variant	Exon 7 of 14		NP_001336891.1
ENTPD7	NM_001349963.2	c.599T>A	p.Phe200Tyr	missense_variant	Exon 6 of 13		NP_001336892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTPD7	ENST00000370489.5	c.599T>A	p.Phe200Tyr	missense_variant	Exon 6 of 13	1	NM_020354.5	ENSP00000359520.4
ENSG00000285932	ENST00000649102.1	n.*539+5764A>T		intron_variant	Intron 9 of 12			ENSP00000497114.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461814 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727218

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.097
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.87	L
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.16
Sift	Benign	0.42	T
Sift4G	Benign	0.65	T
Polyphen		0.055	B
Vest4		0.63
MutPred		0.49		Loss of stability (P = 0.1418);
MVP		0.21
MPC		0.25
ClinPred		0.57	D
GERP RS		5.5
Varity_R		0.37
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr10-101445599;