9-137435226-G-C

Position:

• chr9-137435226-G-C

Variant summary

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

The NM_001033113.2(ENTPD8):​c.1274C>G​(p.Pro425Arg) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ENTPD8 NM_001033113.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.203

Genes affected

ENTPD8 (HGNC:24860): (ectonucleoside triphosphate diphosphohydrolase 8) Predicted to enable guanosine-diphosphatase activity and uridine-diphosphatase activity. Predicted to be involved in nucleoside diphosphate catabolic process. Predicted to act upstream of or within nucleoside diphosphate biosynthetic process and nucleoside monophosphate biosynthetic process. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.09102544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENTPD8	NM_001033113.2	c.1274C>G	p.Pro425Arg	missense_variant	9/10	ENST00000371506.7	NP_001028285.1
ENTPD8	NM_198585.3	c.1163C>G	p.Pro388Arg	missense_variant	8/9		NP_940987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENTPD8	ENST00000371506.7	c.1274C>G	p.Pro425Arg	missense_variant	9/10	5	NM_001033113.2	ENSP00000360561	P1
ENTPD8	ENST00000344119.6	c.1163C>G	p.Pro388Arg	missense_variant	8/9	1		ENSP00000344089
ENTPD8	ENST00000461823.1	n.2072C>G		non_coding_transcript_exon_variant	7/8	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

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

Oct 04, 2022

The c.1274C>G (p.P425R) alteration is located in exon 9 (coding exon 8) of the ENTPD8 gene. This alteration results from a C to G substitution at nucleotide position 1274, causing the proline (P) at amino acid position 425 to be replaced by an arginine (R). 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	0.090
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.85
DEOGEN2	Benign	0.16	.;T;T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.63	T;T;.
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.091	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	.;M;M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Benign	0.048
Sift	Benign	0.30	T;T;T
Sift4G	Benign	0.50	T;T;T
Polyphen		0.65	P;P;P
Vest4		0.30
MutPred		0.44		.;Gain of solvent accessibility (P = 0.0808);Gain of solvent accessibility (P = 0.0808);
MVP		0.072
MPC		0.071
ClinPred		0.35	T
GERP RS		3.4
Varity_R		0.091
gMVP		0.40

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: chr9-140329678;