6-131674272-T-G

Position:

• chr6-131674272-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_005021.5(ENPP3):​c.753T>G​(p.His251Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENPP3 NM_005021.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.39

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]

ENPP3 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.032981455).
• BP6: Variant 6-131674272-T-G is Benign according to our data. Variant chr6-131674272-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2272957.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENPP3	NM_005021.5	c.753T>G	p.His251Gln	missense_variant	8/25	ENST00000357639.8	NP_005012.2
ENPP3	XM_017010932.2	c.522T>G	p.His174Gln	missense_variant	6/23		XP_016866421.1
ENPP3	NR_133007.2	n.836T>G		non_coding_transcript_exon_variant	8/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENPP3	ENST00000357639.8	c.753T>G	p.His251Gln	missense_variant	8/25	1	NM_005021.5	ENSP00000350265.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.0020
DANN	Benign	0.52
DEOGEN2	Benign	0.042	T;T;.
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.52	.;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.033	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N;N;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.2	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.51	T;T;T
Sift4G	Benign	0.54	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.053
MutPred		0.43		Gain of MoRF binding (P = 0.109);Gain of MoRF binding (P = 0.109);Gain of MoRF binding (P = 0.109);
MVP		0.25
MPC		0.061
ClinPred		0.12	T
GERP RS		-11
Varity_R		0.21
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-131995412;