6-131847856-GGTGTGTGTGTGTGTGTGTGTGTGTGT-GGTGTGTGTGTGTGTGT

Position:

• chr6-131847856-GGTGTGTGTGTGTGTGTGTGTGTGTGT-GGTGTGTGTGTGTGTGT

Variant summary

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

The NM_006208.3(ENPP1):​c.313+37_313+46del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,181,986 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: ENPP1 NM_006208.3 intron
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENPP1	NM_006208.3	c.313+37_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+37_313+46del		intron_variant			NM_006208.3	ENSP00000498074	P1
ENPP1	ENST00000513998.5	c.313+37_313+46del		intron_variant, NMD_transcript_variant		5		ENSP00000422424
ENPP1	ENST00000650507.1	c.*149+37_*149+46del		intron_variant, NMD_transcript_variant				ENSP00000497375
ENPP1	ENST00000486853.1	n.333+37_333+46del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000656 AC: 9 AN: 137176 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000854

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000784

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000149 AC: 156 AN: 1044810 Hom.: 0 AF XY: 0.000119 AC XY: 63 AN XY: 529544

Gnomad4 AFR exome AF: 0.000424

Gnomad4 AMR exome AF: 0.0000517

Gnomad4 ASJ exome AF: 0.0000495

Gnomad4 EAS exome AF: 0.000196

Gnomad4 SAS exome AF: 0.0000990

Gnomad4 FIN exome AF: 0.0000253

Gnomad4 NFE exome AF: 0.000159

Gnomad4 OTH exome AF: 0.000132

GnomAD4 genome AF: 0.0000656 AC: 9 AN: 137176 Hom.: 0 Cov.: 0 AF XY: 0.0000900 AC XY: 6 AN XY: 66674

Gnomad4 AFR AF: 0.0000854

Gnomad4 AMR AF: 0.0000721

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000784

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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;