9-137434967-G-C

Variant names:

• chr9-137434967-G-C
• NM_001033113.2:c.1435C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001033113.2(ENTPD8):​c.1435C>G​(p.Leu479Val) 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: -0.303

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057765603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTPD8	NM_001033113.2	c.1435C>G	p.Leu479Val	missense_variant	Exon 10 of 10	ENST00000371506.7	NP_001028285.1
ENTPD8	NM_198585.3	c.1324C>G	p.Leu442Val	missense_variant	Exon 9 of 9		NP_940987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTPD8	ENST00000371506.7	c.1435C>G	p.Leu479Val	missense_variant	Exon 10 of 10	5	NM_001033113.2	ENSP00000360561.2
ENTPD8	ENST00000344119.6	c.1324C>G	p.Leu442Val	missense_variant	Exon 9 of 9	1		ENSP00000344089.2
ENTPD8	ENST00000461823.1	n.2233C>G		non_coding_transcript_exon_variant	Exon 8 of 8	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1435C>G (p.L479V) alteration is located in exon 10 (coding exon 9) of the ENTPD8 gene. This alteration results from a C to G substitution at nucleotide position 1435, causing the leucine (L) at amino acid position 479 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	0.083
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.064	.;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.47	T;T;.
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.058	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	.;M;M
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.82	N;N;N
REVEL	Benign	0.013
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.13	T;T;T
Polyphen		0.13	B;B;B
Vest4		0.14
MutPred		0.30		.;Gain of catalytic residue at L479 (P = 0.0218);Gain of catalytic residue at L479 (P = 0.0218);
MVP		0.030
MPC		0.38
ClinPred		0.092	T
GERP RS		-0.97
Varity_R		0.062
gMVP		0.49

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: chr9-140329419;