10-95711989-G-A

Variant names:

• chr10-95711989-G-A
• rs200247284
• ENST00000453258.6:c.33G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_001098175.2(ENTPD1):​c.33G>A​(p.Gln11Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 1,613,846 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0029 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (21 hom.)
• Consequence: ENTPD1 NM_001098175.2 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.280
• Publications: 1 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 Gene-Disease associations (from GenCC):

• complex hereditary spastic paraplegia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hereditary spastic paraplegia 64

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina, Baylor College of Medicine Research Center, Orphanet
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 10-95711989-G-A is Benign according to our data. Variant chr10-95711989-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 2498467.
• BP7: Synonymous conserved (PhyloP=0.28 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00288 (439/152270) while in subpopulation NFE AF = 0.0052 (354/68024). AF 95% confidence interval is 0.00476. There are 1 homozygotes in GnomAd4. There are 188 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 21 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098175.2. 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
	ENTPD1	NM_001098175.2		c.33G>A	p.Gln11Gln	synonymous	Exon 1 of 10	NP_001091645.1	P49961-2
	ENTPD1	NM_001440933.1		c.33G>A	p.Gln11Gln	synonymous	Exon 4 of 13	NP_001427862.1
	ENTPD1	NM_001440934.1		c.33G>A	p.Gln11Gln	synonymous	Exon 2 of 11	NP_001427863.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD1	ENST00000453258.6	TSL:1	c.33G>A	p.Gln11Gln	synonymous	Exon 1 of 10	ENSP00000390955.2	P49961-2

Frequencies

GnomAD3 genomes AF: 0.00289 AC: 439 AN: 152152 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00520

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00261 AC: 646 AN: 247138 AF XY: 0.00251

Gnomad AFR exome AF: 0.000839

Gnomad AMR exome AF: 0.00278

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000835

Gnomad NFE exome AF: 0.00454

Gnomad OTH exome AF: 0.00265

GnomAD4 exome AF: 0.00498 AC: 7277 AN: 1461576 Hom.: 21 Cov.: 30 AF XY: 0.00488 AC XY: 3549 AN XY: 727114

African (AFR) AF: 0.000687 AC: 23 AN: 33478

American (AMR) AF: 0.00279 AC: 125 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86236

European-Finnish (FIN) AF: 0.00107 AC: 57 AN: 53410

Middle Eastern (MID) AF: 0.000540 AC: 3 AN: 5554

European-Non Finnish (NFE) AF: 0.00616 AC: 6845 AN: 1111972

Other (OTH) AF: 0.00361 AC: 218 AN: 60368

GnomAD4 genome AF: 0.00288 AC: 439 AN: 152270 Hom.: 1 Cov.: 32 AF XY: 0.00253 AC XY: 188 AN XY: 74442

African (AFR) AF: 0.00111 AC: 46 AN: 41550

American (AMR) AF: 0.00177 AC: 27 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10606

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

European-Non Finnish (NFE) AF: 0.00520 AC: 354 AN: 68024

Other (OTH) AF: 0.00379 AC: 8 AN: 2110

Alfa AF: 0.00355 Hom.: 2

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00431

EpiControl AF: 0.00581

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.7
DANN	Benign	0.56
PhyloP100		0.28
PromoterAI		0.021	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200247284; hg19: chr10-97471746;