19-39480608-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The ENST00000544017.5(TIMM50):c.64G>A(p.Gly22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G22G) has been classified as Likely benign.
Frequency
Consequence
ENST00000544017.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
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Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TIMM50 | ENST00000544017.5 | c.64G>A | p.Gly22Ser | missense_variant | 1/11 | 1 | ENSP00000445806 | |||
TIMM50 | ENST00000601358.5 | c.-246G>A | 5_prime_UTR_variant, NMD_transcript_variant | 1/10 | 1 | ENSP00000472476 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152274Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251290Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135812
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461750Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 727174
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152392Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74530
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 15, 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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with TIMM50-related conditions. This variant is present in population databases (rs182488705, gnomAD 0.04%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 22 of the TIMM50 protein (p.Gly22Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at