rs453639

Positions:

• chr6-131728517-C-A
• chr6-131728517-C-G

Variant summary

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

The NM_005021.5(ENPP3):​c.1953+2317C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,088 control chromosomes in the GnomAD database, including 44,618 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 0.75 (44618 hom., cov: 32)
• Consequence: ENPP3 NM_005021.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

Genes affected

ENPP3 (HGNC:3358): (ectonucleotide pyrophosphatase/phosphodiesterase 3) The protein encoded by this gene belongs to a series of ectoenzymes that are involved in hydrolysis of extracellular nucleotides. These ectoenzymes possess ATPase and ATP pyrophosphatase activities and are type II transmembrane proteins. Expression of the related rat mRNA has been found in a subset of immature glial cells and in the alimentary tract. The corresponding rat protein has been detected in the pancreas, small intestine, colon, and liver. The human mRNA is expressed in glioma cells, prostate, and uterus. Expression of the human protein has been detected in uterus, basophils, and mast cells. Two transcript variants, one protein coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENPP3	NM_005021.5	c.1953+2317C>A		intron_variant		ENST00000357639.8
ENPP3	XM_011535897.2	c.1191+2317C>A		intron_variant
ENPP3	XM_017010932.2	c.1722+2317C>A		intron_variant
ENPP3	NR_133007.2	n.2036+2317C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENPP3	ENST00000357639.8	c.1953+2317C>A		intron_variant		1	NM_005021.5	P1
ENPP3	ENST00000358229.6	c.1953+2317C>A		intron_variant		1
ENPP3	ENST00000414305.5	c.1953+2317C>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114565 AN: 151970 Hom.: 44549 Cov.: 32

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.731

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.754 AC: 114694 AN: 152088 Hom.: 44618 Cov.: 32 AF XY: 0.758 AC XY: 56334 AN XY: 74340

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.967

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.734

Alfa AF: 0.651 Hom.: 19289

Bravo AF: 0.769

Asia WGS AF: 0.882 AC: 3068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.2
DANN	Benign	0.66

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: rs453639; hg19: chr6-132049657; COSMIC: COSV62956297;