chr6-131808062-C-G

Position:

• chr6-131808062-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_006208.3(ENPP1):​c.27C>G​(p.Gly9Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENPP1 NM_006208.3 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -0.487

Genes affected

ENPP1 (HGNC:3356): (ectonucleotide pyrophosphatase/phosphodiesterase 1) This gene is a member of the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family. The encoded protein is a type II transmembrane glycoprotein comprising two identical disulfide-bonded subunits. This protein has broad specificity and cleaves a variety of substrates, including phosphodiester bonds of nucleotides and nucleotide sugars and pyrophosphate bonds of nucleotides and nucleotide sugars. This protein may function to hydrolyze nucleoside 5' triphosphates to their corresponding monophosphates and may also hydrolyze diadenosine polyphosphates. Mutations in this gene have been associated with 'idiopathic' infantile arterial calcification, ossification of the posterior longitudinal ligament of the spine (OPLL), and insulin resistance. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 6-131808062-C-G is Benign according to our data. Variant chr6-131808062-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 193333.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
• BP7: Synonymous conserved (PhyloP=-0.487 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENPP1	NM_006208.3	c.27C>G	p.Gly9Gly	synonymous_variant	1/25	ENST00000647893.1	NP_006199.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENPP1	ENST00000647893.1	c.27C>G	p.Gly9Gly	synonymous_variant	1/25		NM_006208.3	ENSP00000498074.1
ENPP1	ENST00000486853.1	n.47C>G		non_coding_transcript_exon_variant	1/4	2
ENPP1	ENST00000513998.5	n.27C>G		non_coding_transcript_exon_variant	1/25	5		ENSP00000422424.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 15 AN: 38368 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.000475

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000998

Gnomad ASJ AF: 0.000984

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000824

Gnomad FIN AF: 0.000633

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000218

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 558104 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 260634

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000365 AC: 14 AN: 38380 Hom.: 0 Cov.: 0 AF XY: 0.000369 AC XY: 7 AN XY: 18984

Gnomad4 AFR AF: 0.000474

Gnomad4 AMR AF: 0.000664

Gnomad4 ASJ AF: 0.000984

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000826

Gnomad4 FIN AF: 0.000633

Gnomad4 NFE AF: 0.000218

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 18, 2015	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	ENPP1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.53

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: rs794726927; hg19: chr6-132129202; COSMIC: COSV62934231;