NM_001247.5:c.*421A>G

Variant names:

• chr20-25226018-A-G
• rs1044573
• NM_001247.5:c.*421A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 46 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ENTPD6	NM_001247.5	c.*421A>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000376652.9	NP_001238.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTPD6	ENST00000376652.9	c.*421A>G		3_prime_UTR_variant	Exon 15 of 15	1	NM_001247.5	ENSP00000365840.4

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

African (AFR) AF: 0.493 AC: 74 AN: 150

American (AMR) AF: 0.313 AC: 136 AN: 434

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 51 AN: 170

East Asian (EAS) AF: 0.934 AC: 185 AN: 198

South Asian (SAS) AF: 0.510 AC: 104 AN: 204

European-Finnish (FIN) AF: 0.515 AC: 100 AN: 194

Middle Eastern (MID) AF: 0.333 AC: 4 AN: 12

European-Non Finnish (NFE) AF: 0.469 AC: 1773 AN: 3782

Other (OTH) AF: 0.454 AC: 158 AN: 348

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

African (AFR) AF: 0.491 AC: 20387 AN: 41504

American (AMR) AF: 0.414 AC: 6321 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1256 AN: 3470

East Asian (EAS) AF: 0.919 AC: 4738 AN: 5154

South Asian (SAS) AF: 0.506 AC: 2435 AN: 4816

European-Finnish (FIN) AF: 0.512 AC: 5427 AN: 10598

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.493 AC: 33547 AN: 67978

Other (OTH) AF: 0.478 AC: 1010 AN: 2112

Alfa AF: 0.477 Hom.: 30738

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
PhyloP100		-0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs1044573; hg19: chr20-25206654;