6-131847856-GGTGTGTGTGTGTGTGTGTGTGTGTGT-GGTGTGTGTGTGTGTGTGT

Position:

• chr6-131847856-GGTGTGTGTGTGTGTGTGTGTGTGTGT-GGTGTGTGTGTGTGTGTGT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_006208.3(ENPP1):​c.313+39_313+46del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000459 in 1,181,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00046 (0 hom.)
• Consequence: ENPP1 NM_006208.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.721

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 6-131847856-GGTGTGTGT-G is Benign according to our data. Variant chr6-131847856-GGTGTGTGT-G is described in ClinVar as [Likely_benign]. Clinvar id is 1114458.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENPP1	NM_006208.3	c.313+39_313+46del		intron_variant		ENST00000647893.1	NP_006199.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENPP1	ENST00000647893.1	c.313+39_313+46del		intron_variant			NM_006208.3	ENSP00000498074	P1
ENPP1	ENST00000513998.5	c.313+39_313+46del		intron_variant, NMD_transcript_variant		5		ENSP00000422424
ENPP1	ENST00000650507.1	c.*149+39_*149+46del		intron_variant, NMD_transcript_variant				ENSP00000497375
ENPP1	ENST00000486853.1	n.333+39_333+46del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.000430 AC: 59 AN: 137174 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000619

Gnomad SAS AF: 0.000471

Gnomad FIN AF: 0.000107

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000188

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000461 AC: 482 AN: 1044632 Hom.: 0 AF XY: 0.000393 AC XY: 208 AN XY: 529460

Gnomad4 AFR exome AF: 0.00480

Gnomad4 AMR exome AF: 0.000336

Gnomad4 ASJ exome AF: 0.0000989

Gnomad4 EAS exome AF: 0.000280

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.000101

Gnomad4 NFE exome AF: 0.000386

Gnomad4 OTH exome AF: 0.000529

GnomAD4 genome AF: 0.000437 AC: 60 AN: 137262 Hom.: 0 Cov.: 0 AF XY: 0.000464 AC XY: 31 AN XY: 66774

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.000216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000621

Gnomad4 SAS AF: 0.000471

Gnomad4 FIN AF: 0.000107

Gnomad4 NFE AF: 0.000188

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 29, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs59956343; hg19: chr6-132168996;