chr1-1535370-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PP3_ModeratePP5
The NM_001114748.2(TMEM240):c.511C>T(p.Arg171Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000904 in 1,549,298 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_001114748.2 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 |
---|---|---|---|---|---|---|---|
TMEM240 | NM_001114748.2 | c.511C>T | p.Arg171Trp | missense_variant | 4/4 | ENST00000378733.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM240 | ENST00000378733.9 | c.511C>T | p.Arg171Trp | missense_variant | 4/4 | 2 | NM_001114748.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152022Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000787 AC: 11AN: 1397276Hom.: 0 Cov.: 33 AF XY: 0.00000435 AC XY: 3AN XY: 689220
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152022Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74252
ClinVar
Submissions by phenotype
Neurodevelopmental disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes | Apr 06, 2020 | - - |
Spinocerebellar ataxia type 21 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 2014 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 14, 2022 | This variant is not present in population databases (gnomAD no frequency). 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 C0"). ClinVar contains an entry for this variant (Variation ID: 161196). This missense change has been observed in individual(s) with autosomal dominant spinocerebellar ataxia (PMID: 25070513). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 171 of the TMEM240 protein (p.Arg171Trp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at