12-56417988-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003920.5(TIMELESS):c.3475G>C(p.Glu1159Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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 Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TIMELESS | NM_003920.5 | c.3475G>C | p.Glu1159Gln | missense_variant | 28/29 | ENST00000553532.6 | |
TIMELESS | NM_001330295.2 | c.3472G>C | p.Glu1158Gln | missense_variant | 28/29 | ||
TIMELESS | NR_138471.2 | n.3612G>C | non_coding_transcript_exon_variant | 28/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TIMELESS | ENST00000553532.6 | c.3475G>C | p.Glu1159Gln | missense_variant | 28/29 | 1 | NM_003920.5 | P4 | |
TIMELESS | ENST00000229201.4 | c.3472G>C | p.Glu1158Gln | missense_variant | 28/29 | 5 | A2 | ||
TIMELESS | ENST00000557589.1 | n.2043G>C | non_coding_transcript_exon_variant | 12/13 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251456Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135900
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727248
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74348
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 26, 2023 | The c.3475G>C (p.E1159Q) alteration is located in exon 28 (coding exon 27) of the TIMELESS gene. This alteration results from a G to C substitution at nucleotide position 3475, causing the glutamic acid (E) at amino acid position 1159 to be replaced by a glutamine (Q). 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