rs1555301559

Variant names:

• chr10-95839723-C-G
• rs1555301559
• NM_001776.6:c.177C>G
• ENTPD1 p.His59Gln

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001776.6(ENTPD1):​c.177C>G​(p.His59Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ENTPD1 NM_001776.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.457
• Publications: 0 publications found

Genes affected

ENTPD1 (HGNC:3363): (ectonucleoside triphosphate diphosphohydrolase 1) The protein encoded by this gene is a plasma membrane protein that hydrolyzes extracellular ATP and ADP to AMP. Inhibition of this protein's activity may confer anticancer benefits. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

ENTPD1-AS1 (HGNC:45203): (ENTPD1 antisense RNA 1)

ENSG00000240527 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.928

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001776.6. 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
	ENTPD1	NM_001776.6	MANE Select	c.177C>G	p.His59Gln	missense	Exon 3 of 10	NP_001767.3
	ENTPD1	NM_001440932.1		c.255C>G	p.His85Gln	missense	Exon 3 of 10	NP_001427861.1
	ENTPD1	NM_001164178.1		c.213C>G	p.His71Gln	missense	Exon 3 of 10	NP_001157650.1	P49961-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD1	ENST00000371205.5	TSL:1 MANE Select	c.177C>G	p.His59Gln	missense	Exon 3 of 10	ENSP00000360248.4	P49961-1
	ENTPD1	ENST00000453258.6	TSL:1	c.198C>G	p.His66Gln	missense	Exon 3 of 10	ENSP00000390955.2	P49961-2
	ENTPD1	ENST00000635076.1	TSL:1	n.145-4753C>G		intron	N/A	ENSP00000489250.1	A0A0U1RQZ5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461880 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Hereditary spastic paraplegia 64 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.8	H
PhyloP100		0.46
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-7.1	D
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.011	D
Varity_R		0.88
gMVP		0.87
Mutation Taster		=28/72	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1555301559;

hg19: chr10-97599480;