12-56420675-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003920.5(TIMELESS):c.3122C>G(p.Ala1041Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
TIMELESS
NM_003920.5 missense
NM_003920.5 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 6.41
Genes affected
TIMELESS (HGNC:11813): (timeless circadian regulator) The protein encoded by this gene is highly conserved and is involved in cell survival after damage or stress, increase in DNA polymerase epsilon activity, maintenance of telomere length, and epithelial cell morphogenesis. The encoded protein also plays a role in the circadian rhythm autoregulatory loop, interacting with the PERIOD genes (PER1, PER2, and PER3) and others to downregulate activation of PER1 by CLOCK/ARNTL. Changes in this gene or its expression may promote prostate cancer, lung cancer, breast cancer, and mental disorders. [provided by RefSeq, Feb 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.24967271).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TIMELESS | NM_003920.5 | c.3122C>G | p.Ala1041Gly | missense_variant | 26/29 | ENST00000553532.6 | |
TIMELESS | NM_001330295.2 | c.3119C>G | p.Ala1040Gly | missense_variant | 26/29 | ||
TIMELESS | NR_138471.2 | n.3259C>G | non_coding_transcript_exon_variant | 26/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TIMELESS | ENST00000553532.6 | c.3122C>G | p.Ala1041Gly | missense_variant | 26/29 | 1 | NM_003920.5 | P4 | |
TIMELESS | ENST00000229201.4 | c.3119C>G | p.Ala1040Gly | missense_variant | 26/29 | 5 | A2 | ||
TIMELESS | ENST00000553314.1 | n.335C>G | non_coding_transcript_exon_variant | 2/3 | 3 | ||||
TIMELESS | ENST00000557589.1 | n.1690C>G | non_coding_transcript_exon_variant | 10/13 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 12, 2021 | The c.3122C>G (p.A1041G) alteration is located in exon 26 (coding exon 25) of the TIMELESS gene. This alteration results from a C to G substitution at nucleotide position 3122, causing the alanine (A) at amino acid position 1041 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Uncertain
T;T
Polyphen
B;.
Vest4
MutPred
Gain of catalytic residue at V1045 (P = 9e-04);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.