chr17-81511470-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_Strong
The NM_001614.5(ACTG1):c.520G>A(p.Ala174Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,542 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 Uncertain significance (★).
Frequency
Consequence
NM_001614.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACTG1 | NM_001614.5 | c.520G>A | p.Ala174Thr | missense_variant | 4/6 | ENST00000573283.7 | NP_001605.1 | |
ACTG1 | NM_001199954.3 | c.520G>A | p.Ala174Thr | missense_variant | 4/6 | NP_001186883.1 | ||
ACTG1 | NR_037688.3 | n.592G>A | non_coding_transcript_exon_variant | 4/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACTG1 | ENST00000573283.7 | c.520G>A | p.Ala174Thr | missense_variant | 4/6 | 5 | NM_001614.5 | ENSP00000458435 | P4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461542Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0AN XY: 727072
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Autosomal dominant nonsyndromic hearing loss 20 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Victorian Clinical Genetics Services, Murdoch Childrens Research Institute | Oct 19, 2020 | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3B-VUS. Following criteria are met: 0101 - Gain-of-function is a known mechanism of disease for this gene. (N) 0107 - This gene is known to be associated with autosomal dominant disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from alanine to threonine (exon 4). (N) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0309 - An alternative amino acid change at the same position has been observed in gnomAD v2 (1 heterozygote, 0 homozygotes). (N) 0502 - Missense variant with conflicting in silico predictions and/or uninformative conservation. (N) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region) (actin domain; PDB). (P) 0705 - No comparable variants have previous evidence for pathogenicity. Alternative changes at the same residue (p.Ala174Ser, p.Ala174Gly) have been reported as VUS (ClinVar, deafnessvariationdatabase, LOVD, PMID: 29907799). (N) 0807 - Variant has not previously been reported in a clinical context. (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.