12-56421040-C-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_003920.5(TIMELESS):c.2963G>C(p.Gly988Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,614,180 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 (★).
Frequency
Consequence
NM_003920.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TIMELESS | NM_003920.5 | c.2963G>C | p.Gly988Ala | missense_variant | 24/29 | ENST00000553532.6 | |
TIMELESS | NM_001330295.2 | c.2960G>C | p.Gly987Ala | missense_variant | 24/29 | ||
TIMELESS | NR_138471.2 | n.3100G>C | non_coding_transcript_exon_variant | 24/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TIMELESS | ENST00000553532.6 | c.2963G>C | p.Gly988Ala | missense_variant | 24/29 | 1 | NM_003920.5 | P4 | |
TIMELESS | ENST00000229201.4 | c.2960G>C | p.Gly987Ala | missense_variant | 24/29 | 5 | A2 | ||
TIMELESS | ENST00000553314.1 | n.51G>C | non_coding_transcript_exon_variant | 1/3 | 3 | ||||
TIMELESS | ENST00000557589.1 | n.1531G>C | non_coding_transcript_exon_variant | 8/13 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152168Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251482Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135916
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461894Hom.: 0 Cov.: 37 AF XY: 0.0000138 AC XY: 10AN XY: 727248
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152286Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74464
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 31, 2024 | The c.2963G>C (p.G988A) alteration is located in exon 24 (coding exon 23) of the TIMELESS gene. This alteration results from a G to C substitution at nucleotide position 2963, causing the glycine (G) at amino acid position 988 to be replaced by an alanine (A). 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