chr7-12214938-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001134232.2(TMEM106B):c.128G>C(p.Gly43Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000867 in 1,613,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G43E) has been classified as Uncertain significance.
Frequency
Consequence
NM_001134232.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM106B | NM_001134232.2 | c.128G>C | p.Gly43Ala | missense_variant | 2/8 | ENST00000396668.8 | |
TMEM106B | NM_018374.4 | c.128G>C | p.Gly43Ala | missense_variant | 3/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM106B | ENST00000396668.8 | c.128G>C | p.Gly43Ala | missense_variant | 2/8 | 1 | NM_001134232.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251358Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135848
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461752Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727172
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74386
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with TMEM106B-related conditions. This variant is present in population databases (rs137861973, gnomAD 0.009%). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 43 of the TMEM106B protein (p.Gly43Ala). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at