rs121908249
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_006208.3(ENPP1):āc.2702A>Cā(p.Tyr901Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000656 in 152,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Consequence
ENPP1
NM_006208.3 missense
NM_006208.3 missense
Scores
11
6
1
Clinical Significance
Conservation
PhyloP100: 4.13
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.971
PP5
?
Variant 6-131890435-A-C is Pathogenic according to our data. Variant chr6-131890435-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 13596.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-131890435-A-C is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENPP1 | NM_006208.3 | c.2702A>C | p.Tyr901Ser | missense_variant | 25/25 | ENST00000647893.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENPP1 | ENST00000647893.1 | c.2702A>C | p.Tyr901Ser | missense_variant | 25/25 | NM_006208.3 | P1 | ||
ENPP1 | ENST00000684674.1 | n.1133A>C | non_coding_transcript_exon_variant | 6/6 | |||||
ENPP1 | ENST00000513998.5 | c.*1539A>C | 3_prime_UTR_variant, NMD_transcript_variant | 25/25 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152254Hom.: 0 Cov.: 32
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GnomAD4 exome Cov.: 30
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GnomAD4 genome ? AF: 0.00000656 AC: 1AN: 152372Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74520
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hypophosphatemic rickets, autosomal recessive, 2 Pathogenic:1Other:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 12, 2010 | - - |
not provided, no classification provided | literature only | UniProtKB/Swiss-Prot | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
A
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.
REVEL
Pathogenic
Sift
Pathogenic
D;.
Sift4G
Uncertain
D;.
Polyphen
D;D
Vest4
MutPred
Gain of disorder (P = 0.0052);Gain of disorder (P = 0.0052);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at