rs12199015

Variant names:

• chr6-131737807-A-G
• rs12199015
• NM_005021.5:c.2168-224A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005021.5(ENPP3):​c.2168-224A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0695 in 152,228 control chromosomes in the GnomAD database, including 824 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 0.069 (824 hom., cov: 32)
• Consequence: ENPP3 NM_005021.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENPP3	NM_005021.5	c.2168-224A>G		intron_variant	Intron 22 of 24	ENST00000357639.8	NP_005012.2
ENPP3	NR_133007.2	n.2115-224A>G		intron_variant	Intron 21 of 23
ENPP3	XM_017010932.2	c.1937-224A>G		intron_variant	Intron 20 of 22		XP_016866421.1
ENPP3	XM_011535897.2	c.1406-224A>G		intron_variant	Intron 15 of 17		XP_011534199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENPP3	ENST00000357639.8	c.2168-224A>G		intron_variant	Intron 22 of 24	1	NM_005021.5	ENSP00000350265.3
ENPP3	ENST00000414305.5	c.2168-224A>G		intron_variant	Intron 23 of 25	1		ENSP00000406261.1
ENPP3	ENST00000358229.6	c.*40-224A>G		intron_variant	Intron 21 of 23	1		ENSP00000350964.5

Frequencies

GnomAD3 genomes AF: 0.0694 AC: 10554 AN: 152108 Hom.: 823 Cov.: 32

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0568

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0522

Gnomad OTH AF: 0.0570

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

GnomAD4 genome AF: 0.0695 AC: 10578 AN: 152228 Hom.: 824 Cov.: 32 AF XY: 0.0748 AC XY: 5567 AN XY: 74422

African (AFR) AF: 0.0221 AC: 918 AN: 41564

American (AMR) AF: 0.184 AC: 2812 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 170 AN: 3468

East Asian (EAS) AF: 0.326 AC: 1685 AN: 5172

South Asian (SAS) AF: 0.141 AC: 679 AN: 4826

European-Finnish (FIN) AF: 0.0568 AC: 603 AN: 10610

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0523 AC: 3554 AN: 67992

Other (OTH) AF: 0.0583 AC: 123 AN: 2110

Alfa AF: 0.0781 Hom.: 125

Bravo AF: 0.0772

Asia WGS AF: 0.181 AC: 629 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.5
DANN	Benign	0.79
PhyloP100		0.15
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: rs12199015; hg19: chr6-132058947; COSMIC: COSV62955495;