chr12-56418000-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_003920.5(TIMELESS):c.3463G>A(p.Ala1155Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,614,202 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1155D) has been classified as Uncertain significance.
Frequency
Consequence
NM_003920.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TIMELESS | NM_003920.5 | c.3463G>A | p.Ala1155Thr | missense_variant | 28/29 | ENST00000553532.6 | |
TIMELESS | NM_001330295.2 | c.3460G>A | p.Ala1154Thr | missense_variant | 28/29 | ||
TIMELESS | NR_138471.2 | n.3600G>A | non_coding_transcript_exon_variant | 28/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TIMELESS | ENST00000553532.6 | c.3463G>A | p.Ala1155Thr | missense_variant | 28/29 | 1 | NM_003920.5 | P4 | |
TIMELESS | ENST00000229201.4 | c.3460G>A | p.Ala1154Thr | missense_variant | 28/29 | 5 | A2 | ||
TIMELESS | ENST00000557589.1 | n.2031G>A | non_coding_transcript_exon_variant | 12/13 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000677 AC: 103AN: 152190Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000155 AC: 39AN: 251468Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135908
GnomAD4 exome AF: 0.0000691 AC: 101AN: 1461894Hom.: 0 Cov.: 32 AF XY: 0.0000688 AC XY: 50AN XY: 727248
GnomAD4 genome ? AF: 0.000676 AC: 103AN: 152308Hom.: 0 Cov.: 31 AF XY: 0.000698 AC XY: 52AN XY: 74478
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 23, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at