20-37996946-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001303457.2(TTI1):c.2801G>A(p.Arg934His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00008 in 1,613,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. R934C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001303457.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTI1 | NM_001303457.2 | c.2801G>A | p.Arg934His | missense_variant | 6/8 | ENST00000373447.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTI1 | ENST00000373447.8 | c.2801G>A | p.Arg934His | missense_variant | 6/8 | 1 | NM_001303457.2 | P1 | |
TTI1 | ENST00000373448.6 | c.2801G>A | p.Arg934His | missense_variant | 7/9 | 1 | P1 | ||
TTI1 | ENST00000449821.1 | c.2801G>A | p.Arg934His | missense_variant | 5/7 | 2 | P1 | ||
TTI1 | ENST00000473288.1 | n.260G>A | non_coding_transcript_exon_variant | 3/4 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000415 AC: 63AN: 151980Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000759 AC: 19AN: 250284Hom.: 0 AF XY: 0.0000591 AC XY: 8AN XY: 135274
GnomAD4 exome AF: 0.0000452 AC: 66AN: 1461056Hom.: 0 Cov.: 31 AF XY: 0.0000454 AC XY: 33AN XY: 726708
GnomAD4 genome AF: 0.000414 AC: 63AN: 152098Hom.: 0 Cov.: 32 AF XY: 0.000377 AC XY: 28AN XY: 74330
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2021 | The c.2801G>A (p.R934H) alteration is located in exon 7 (coding exon 5) of the TTI1 gene. This alteration results from a G to A substitution at nucleotide position 2801, causing the arginine (R) at amino acid position 934 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at