9-137435301-C-T

Variant names:

• chr9-137435301-C-T
• rs78674871
• NM_001033113.2:c.1199G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001033113.2(ENTPD8):​c.1199G>A​(p.Arg400Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,612,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R400W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: ENTPD8 NM_001033113.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.02
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03437051).

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.1199G>A	p.Arg400Gln	missense	Exon 9 of 10	NP_001028285.1	Q5MY95-1
	ENTPD8	NM_198585.3		c.1088G>A	p.Arg363Gln	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.1199G>A	p.Arg400Gln	missense	Exon 9 of 10	ENSP00000360561.2	Q5MY95-1
	ENTPD8	ENST00000344119.6	TSL:1	c.1088G>A	p.Arg363Gln	missense	Exon 8 of 9	ENSP00000344089.2	Q5MY95-2
	ENTPD8	ENST00000881602.1		c.1199G>A	p.Arg400Gln	missense	Exon 10 of 11	ENSP00000551661.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152234 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000241 AC: 6 AN: 248490 AF XY: 0.0000296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000870

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1459962 Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13 AN XY: 726292

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.0000895 AC: 4 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51936

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5654

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111808

Other (OTH) AF: 0.0000331 AC: 2 AN: 60342

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152352 Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3 AN XY: 74496

African (AFR) AF: 0.0000722 AC: 3 AN: 41580

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.10
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	10
DANN	Benign	0.96
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		-2.0
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.0060
Sift	Benign	0.32	T
Sift4G	Benign	0.67	T
Polyphen		0.48	P
Vest4		0.14
MVP		0.014
MPC		0.072
ClinPred		0.12	T
GERP RS		0.77
Varity_R		0.047
gMVP		0.30
Mutation Taster		=94/6	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: rs78674871; hg19: chr9-140329753;