7-19116792-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_000474.4(TWIST1):c.530A>G(p.Tyr177Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,768 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y177S) has been classified as Uncertain significance.
Frequency
Consequence
NM_000474.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TWIST1 | NM_000474.4 | c.530A>G | p.Tyr177Cys | missense_variant | 1/2 | ENST00000242261.6 | |
TWIST1 | NR_149001.2 | n.845A>G | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TWIST1 | ENST00000242261.6 | c.530A>G | p.Tyr177Cys | missense_variant | 1/2 | 1 | NM_000474.4 | P1 | |
TWIST1 | ENST00000354571.5 | c.329A>G | p.Tyr110Cys | missense_variant, NMD_transcript_variant | 1/3 | 2 | |||
TWIST1 | ENST00000443687.5 | c.134A>G | p.Tyr45Cys | missense_variant, NMD_transcript_variant | 1/4 | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250248Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135576
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461768Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727188
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 10, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); 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