rs372686071
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BP6
The NM_001044385.3(TMEM237):āc.1024A>Gā(p.Asn342Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000442 in 1,606,372 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001044385.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM237 | NM_001044385.3 | c.1024A>G | p.Asn342Asp | missense_variant | 11/13 | ENST00000409883.7 | |
TMEM237 | NM_152388.4 | c.1000A>G | p.Asn334Asp | missense_variant | 11/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM237 | ENST00000409883.7 | c.1024A>G | p.Asn342Asp | missense_variant | 11/13 | 5 | NM_001044385.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000583 AC: 14AN: 240076Hom.: 0 AF XY: 0.0000231 AC XY: 3AN XY: 129648
GnomAD4 exome AF: 0.0000454 AC: 66AN: 1454152Hom.: 0 Cov.: 30 AF XY: 0.0000457 AC XY: 33AN XY: 722604
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74364
ClinVar
Submissions by phenotype
Joubert syndrome 14 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 03, 2022 | 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 257313). This variant has not been reported in the literature in individuals affected with TMEM237-related conditions. This variant is present in population databases (rs372686071, gnomAD 0.009%). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 342 of the TMEM237 protein (p.Asn342Asp). - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Joubert syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at