rs774033

Variant names:

• chr12-56431527-C-G
• rs774033
• NM_003920.5:c.765G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-56431527-C-G
• chr12-56431527-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003920.5(TIMELESS):​c.765G>C​(p.Val255Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 29)
• Consequence: TIMELESS NM_003920.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480
• Publications: 31 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=-0.48 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMELESS	NM_003920.5	c.765G>C	p.Val255Val	synonymous_variant	Exon 8 of 29	ENST00000553532.6	NP_003911.2
TIMELESS	NM_001330295.2	c.762G>C	p.Val254Val	synonymous_variant	Exon 8 of 29		NP_001317224.1
TIMELESS	NR_138471.2	n.943G>C		non_coding_transcript_exon_variant	Exon 8 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMELESS	ENST00000553532.6	c.765G>C	p.Val255Val	synonymous_variant	Exon 8 of 29	1	NM_003920.5	ENSP00000450607.1
TIMELESS	ENST00000229201.4	c.762G>C	p.Val254Val	synonymous_variant	Exon 8 of 29	5		ENSP00000229201.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 33672

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.4
DANN	Benign	0.59
PhyloP100		-0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs774033; hg19: chr12-56825311;