rs775442178
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_001114753.3(ENG):c.578C>T(p.Thr193Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000282 in 1,597,196 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T193A) has been classified as Uncertain significance.
Frequency
Consequence
NM_001114753.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.578C>T | p.Thr193Met | missense_variant | 5/15 | ENST00000373203.9 | |
ENG | NM_000118.4 | c.578C>T | p.Thr193Met | missense_variant | 5/14 | ||
ENG | NM_001278138.2 | c.32C>T | p.Thr11Met | missense_variant | 5/15 | ||
ENG | NM_001406715.1 | c.578C>T | p.Thr193Met | missense_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENG | ENST00000373203.9 | c.578C>T | p.Thr193Met | missense_variant | 5/15 | 1 | NM_001114753.3 | P2 | |
ENG | ENST00000344849.4 | c.578C>T | p.Thr193Met | missense_variant | 5/14 | 1 | A2 | ||
ENG | ENST00000480266.6 | c.32C>T | p.Thr11Met | missense_variant | 5/15 | 2 | |||
ENG | ENST00000462196.1 | n.478C>T | non_coding_transcript_exon_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000702 AC: 15AN: 213802Hom.: 0 AF XY: 0.0000599 AC XY: 7AN XY: 116860
GnomAD4 exome AF: 0.0000304 AC: 44AN: 1445050Hom.: 1 Cov.: 35 AF XY: 0.0000265 AC XY: 19AN XY: 717352
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74316
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 22, 2020 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 458349; Landrum et al., 2016) - |
Hereditary hemorrhagic telangiectasia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at