17-81510698-A-T
Variant summary
Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001614.5(ACTG1):c.1120T>A(p.Cys374Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. C374Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_001614.5 missense
Scores
Clinical Significance
Conservation
Publications
- Baraitser-winter syndrome 2Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
- nonsyndromic genetic hearing lossInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- autosomal dominant nonsyndromic hearing loss 20Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
- autosomal dominant nonsyndromic hearing lossInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Baraitser-Winter cerebrofrontofacial syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_pathogenic. The variant received 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACTG1 | NM_001614.5 | c.1120T>A | p.Cys374Ser | missense_variant | Exon 6 of 6 | ENST00000573283.7 | NP_001605.1 | |
ACTG1 | NM_001199954.3 | c.1120T>A | p.Cys374Ser | missense_variant | Exon 6 of 6 | NP_001186883.1 | ||
ACTG1 | NR_037688.3 | n.1192T>A | non_coding_transcript_exon_variant | Exon 6 of 7 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at