2-70212795-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP5BP4BS2
The NM_022173.4(TIA1):c.1085C>T(p.Pro362Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000205 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_022173.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251444Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135894
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461824Hom.: 0 Cov.: 30 AF XY: 0.0000289 AC XY: 21AN XY: 727222
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
AMYOTROPHIC LATERAL SCLEROSIS 26 WITH FRONTOTEMPORAL DEMENTIA Pathogenic:1
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not provided Pathogenic:1
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Welander distal myopathy Uncertain:1
This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 362 of the TIA1 protein (p.Pro362Leu). This variant is present in population databases (rs757332023, gnomAD 0.01%). This missense change has been observed in individual(s) with amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD) and dementia with Lewy bodies (PMID: 28817800, 31996268). ClinVar contains an entry for this variant (Variation ID: 992595). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Experimental studies have shown that this missense change affects TIA1 function (PMID: 28817800, 36112647). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at