9-116698784-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_012210.4(TRIM32):c.1042G>T(p.Ala348Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_012210.4 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRIM32 | NM_012210.4 | c.1042G>T | p.Ala348Ser | missense_variant | Exon 2 of 2 | ENST00000450136.2 | NP_036342.2 | |
ASTN2 | NM_001365068.1 | c.2806+26987C>A | intron_variant | Intron 16 of 22 | ENST00000313400.9 | NP_001351997.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRIM32 | ENST00000450136.2 | c.1042G>T | p.Ala348Ser | missense_variant | Exon 2 of 2 | 1 | NM_012210.4 | ENSP00000408292.1 | ||
ASTN2 | ENST00000313400.9 | c.2806+26987C>A | intron_variant | Intron 16 of 22 | 5 | NM_001365068.1 | ENSP00000314038.4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251274Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135826
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461872Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727236
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74350
ClinVar
Submissions by phenotype
Bardet-Biedl syndrome Uncertain:1
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 do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). This variant has not been reported in the literature in individuals with TRIM32-related disease. This variant is present in population databases (rs771427815, ExAC 0.01%). This sequence change replaces alanine with serine at codon 348 of the TRIM32 protein (p.Ala348Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at