chr9-137435226-G-C

Variant names:

• chr9-137435226-G-C
• rs1409650051
• NM_001033113.2:c.1274C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09102544).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033113.2. 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
	ENTPD8	NM_001033113.2	MANE Select	c.1274C>G	p.Pro425Arg	missense	Exon 9 of 10	NP_001028285.1	Q5MY95-1
	ENTPD8	NM_198585.3		c.1163C>G	p.Pro388Arg	missense	Exon 8 of 9	NP_940987.2	Q5MY95-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD8	ENST00000371506.7	TSL:5 MANE Select	c.1274C>G	p.Pro425Arg	missense	Exon 9 of 10	ENSP00000360561.2	Q5MY95-1
	ENTPD8	ENST00000344119.6	TSL:1	c.1163C>G	p.Pro388Arg	missense	Exon 8 of 9	ENSP00000344089.2	Q5MY95-2
	ENTPD8	ENST00000881602.1		c.1274C>G	p.Pro425Arg	missense	Exon 10 of 11	ENSP00000551661.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

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	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
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.20
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.048
Sift	Benign	0.30	T
Sift4G	Benign	0.50	T
Polyphen		0.65	P
Vest4		0.30
MutPred		0.44		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
Mutation Taster		=92/8	polymorphism

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

dbSNP: rs1409650051; hg19: chr9-140329678;