chr6-131847856-G-GGTGTGTGT

Position:

• chr6-131847856-G-GGTGTGTGT

Variant summary

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

The NM_006208.3(ENPP1):​c.313+39_313+46dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00031 (0 hom.)
• Consequence: ENPP1 NM_006208.3 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.525

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.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 180 AN: 137176 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00439

Gnomad EAS AF: 0.000413

Gnomad SAS AF: 0.00141

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000298

Gnomad OTH AF: 0.00272

GnomAD4 exome AF: 0.000313 AC: 327 AN: 1044650 Hom.: 0 Cov.: 14 AF XY: 0.000323 AC XY: 171 AN XY: 529456

Gnomad4 AFR exome AF: 0.000806

Gnomad4 AMR exome AF: 0.000466

Gnomad4 ASJ exome AF: 0.00238

Gnomad4 EAS exome AF: 0.0000840

Gnomad4 SAS exome AF: 0.000382

Gnomad4 FIN exome AF: 0.000177

Gnomad4 NFE exome AF: 0.000244

Gnomad4 OTH exome AF: 0.000353

GnomAD4 genome AF: 0.00131 AC: 180 AN: 137264 Hom.: 1 Cov.: 0 AF XY: 0.00126 AC XY: 84 AN XY: 66772

Gnomad4 AFR AF: 0.00324

Gnomad4 AMR AF: 0.00151

Gnomad4 ASJ AF: 0.00439

Gnomad4 EAS AF: 0.000414

Gnomad4 SAS AF: 0.00141

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000298

Gnomad4 OTH AF: 0.00269

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 29, 2021

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with ENPP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 2 of the ENPP1 gene. It does not directly change the encoded amino acid sequence of the ENPP1 protein. -

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;