rs753071702
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_006208.3(ENPP1):c.1652A>G(p.Tyr551Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. Y551Y) has been classified as Likely benign.
Frequency
Consequence
NM_006208.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENPP1 | NM_006208.3 | c.1652A>G | p.Tyr551Cys | missense_variant | 17/25 | ENST00000647893.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENPP1 | ENST00000647893.1 | c.1652A>G | p.Tyr551Cys | missense_variant | 17/25 | NM_006208.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251278Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135802
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461662Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727154
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74358
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 11, 2023 | ClinVar contains an entry for this variant (Variation ID: 561004). This missense change has been observed in individuals with autosomal recessive ENPP1-related conditions (PMID: 25326635, 33005041; Invitae). This variant is present in population databases (rs753071702, gnomAD 0.006%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 551 of the ENPP1 protein (p.Tyr551Cys). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ENPP1 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 22, 2023 | - - |
Arterial calcification, generalized, of infancy, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 01, 2017 | Likely pathogenicity based on finding it once in our laboratory in trans with another missense variant in a 1-year-old male with fibromuscular dysplasia, coarctation, low sodium level, cardiomyopathy, hypertension, seizures - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at