rs1044498
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_006208.3(ENPP1):āc.517A>Cā(p.Lys173Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,613,790 control chromosomes in the GnomAD database, including 41,008 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Consequence
NM_006208.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ENPP1 | NM_006208.3 | c.517A>C | p.Lys173Gln | missense_variant | 4/25 | ENST00000647893.1 | NP_006199.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ENPP1 | ENST00000647893.1 | c.517A>C | p.Lys173Gln | missense_variant | 4/25 | NM_006208.3 | ENSP00000498074 | P1 |
Frequencies
GnomAD3 genomes AF: 0.328 AC: 49878AN: 152022Hom.: 14135 Cov.: 32
GnomAD3 exomes AF: 0.195 AC: 48946AN: 251206Hom.: 8046 AF XY: 0.183 AC XY: 24803AN XY: 135756
GnomAD4 exome AF: 0.162 AC: 236113AN: 1461650Hom.: 26814 Cov.: 33 AF XY: 0.159 AC XY: 115934AN XY: 727146
GnomAD4 genome AF: 0.329 AC: 49999AN: 152140Hom.: 14194 Cov.: 32 AF XY: 0.322 AC XY: 23968AN XY: 74384
ClinVar
Submissions by phenotype
Hypophosphatemic rickets, autosomal recessive, 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Arterial calcification, generalized, of infancy, 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Hypophosphatemic rickets Pathogenic:1
Likely pathogenic, flagged submission | clinical testing | Laboratory of Cyto-molecular Genetics, Department of Anatomy, All India Institute of Medical Sciences (AIIMS), New Delhi | Mar 07, 2022 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 24, 2015 | - - |
Type 2 diabetes mellitus Benign:1
Benign, criteria provided, single submitter | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | rs1044498 of ENPP1 is associated with type 2 diabetes mellitus and increased insulin resistance. It is also associated with calcification of coronary artery disease, increasing the chances of macrovascular complications in diabetes. - |
Hypopigmentation-punctate palmoplantar keratoderma syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
ENPP1-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 23, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Insulin resistance, susceptibility to Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Aug 15, 2016 | - - |
Diabetes mellitus type 2, susceptibility to Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Dec 01, 2006 | - - |
Obesity Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Dec 01, 2006 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at