20-25226018-A-G

Position:

• chr20-25226018-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001247.5(ENTPD6):​c.*421A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 157,614 control chromosomes in the GnomAD database, including 20,137 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.50 (19460 hom., cov: 34)
  • Exomes 𝑓: 0.47 (677 hom.)
• Consequence: ENTPD6 NM_001247.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.988

Genes affected

ENTPD6 (HGNC:3368): (ectonucleoside triphosphate diphosphohydrolase 6) ENTPD6 is similar to E-type nucleotidases (NTPases). NTPases, such as CD39, mediate catabolism of extracellular nucleotides. ENTPD6 contains 4 apyrase-conserved regions which are characteristic of NTPases. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENTPD6	NM_001247.5	c.*421A>G		3_prime_UTR_variant	15/15	ENST00000376652.9	NP_001238.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENTPD6	ENST00000376652.9	c.*421A>G		3_prime_UTR_variant	15/15	1	NM_001247.5	ENSP00000365840	P4

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75704 AN: 152004 Hom.: 19447 Cov.: 34

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.477

GnomAD4 exome AF: 0.471 AC: 2585 AN: 5492 Hom.: 677 Cov.: 0 AF XY: 0.465 AC XY: 1312 AN XY: 2820

Gnomad4 AFR exome AF: 0.493

Gnomad4 AMR exome AF: 0.313

Gnomad4 ASJ exome AF: 0.300

Gnomad4 EAS exome AF: 0.934

Gnomad4 SAS exome AF: 0.510

Gnomad4 FIN exome AF: 0.515

Gnomad4 NFE exome AF: 0.469

Gnomad4 OTH exome AF: 0.454

GnomAD4 genome AF: 0.498 AC: 75741 AN: 152122 Hom.: 19460 Cov.: 34 AF XY: 0.501 AC XY: 37222 AN XY: 74360

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.919

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.493

Gnomad4 OTH AF: 0.478

Alfa AF: 0.472 Hom.: 21930

Bravo AF: 0.488

Asia WGS AF: 0.689 AC: 2393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

dbSNP: rs1044573; hg19: chr20-25206654;