Variant chr12-56431527-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_003920.5(TIMELESS):c.765G>A(p.Val255Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 1,612,506 control chromosomes in the GnomAD database, including 171,672 homozygotes. 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: 𝑓 0.42 ( 14747 hom., cov: 29)

Exomes 𝑓: 0.46 ( 156925 hom. )

Consequence

TIMELESS
NM_003920.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.480

Variant links:

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]

TIMELESS links:

TIMELESS (HGNC:):

TIMELESS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP7

Synonymous conserved (PhyloP=-0.48 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIMELESS	NM_003920.5 linkuse as main transcript	c.765G>A	p.Val255Val	synonymous_variant	8/29	ENST00000553532.6	NP_003911.2	Q9UNS1-1
TIMELESS	NM_001330295.2 linkuse as main transcript	c.762G>A	p.Val254Val	synonymous_variant	8/29		NP_001317224.1	Q9UNS1-2
TIMELESS	NR_138471.2 linkuse as main transcript	n.943G>A		non_coding_transcript_exon_variant	8/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMELESS	ENST00000553532.6 linkuse as main transcript	c.765G>A	p.Val255Val	synonymous_variant	8/29	1	NM_003920.5	ENSP00000450607.1		Q9UNS1-1
TIMELESS	ENST00000229201.4 linkuse as main transcript	c.762G>A	p.Val254Val	synonymous_variant	8/29	5		ENSP00000229201.4		Q9UNS1-2

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

63965

AN:

151638

Hom.:

14741

Cov.:

show subpopulations

Gnomad AFR

AF:

0.265

Gnomad AMI

AF:

0.387

Gnomad AMR

AF:

0.579

Gnomad ASJ

AF:

0.530

Gnomad EAS

AF:

0.728

Gnomad SAS

AF:

0.499

Gnomad FIN

AF:

0.405

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.448

Gnomad OTH

AF:

0.495

GnomAD3 exomes

AF:

0.504

AC:

126334

AN:

250534

Hom.:

34164

AF XY:

0.499

AC XY:

67623

AN XY:

135460

show subpopulations

Gnomad AFR exome

AF:

0.258

Gnomad AMR exome

AF:

0.713

Gnomad ASJ exome

AF:

0.523

Gnomad EAS exome

AF:

0.743

Gnomad SAS exome

AF:

0.497

Gnomad FIN exome

AF:

0.416

Gnomad NFE exome

AF:

0.455

Gnomad OTH exome

AF:

0.505

GnomAD4 exome

AF:

0.457

AC:

667604

AN:

1460750

Hom.:

156925

Cov.:

AF XY:

0.458

AC XY:

332749

AN XY:

726712

show subpopulations

Gnomad4 AFR exome

AF:

0.253

Gnomad4 AMR exome

AF:

0.699

Gnomad4 ASJ exome

AF:

0.527

Gnomad4 EAS exome

AF:

0.671

Gnomad4 SAS exome

AF:

0.496

Gnomad4 FIN exome

AF:

0.423

Gnomad4 NFE exome

AF:

0.441

Gnomad4 OTH exome

AF:

0.472

GnomAD4 genome

AF:

0.422

AC:

63986

AN:

151756

Hom.:

14747

Cov.:

AF XY:

0.425

AC XY:

31495

AN XY:

74146

show subpopulations

Gnomad4 AFR

AF:

0.265

Gnomad4 AMR

AF:

0.580

Gnomad4 ASJ

AF:

0.530

Gnomad4 EAS

AF:

0.727

Gnomad4 SAS

AF:

0.499

Gnomad4 FIN

AF:

0.405

Gnomad4 NFE

AF:

0.448

Gnomad4 OTH

AF:

0.490

Alfa

AF:

0.462

Hom.:

28174

Bravo

AF:

0.438

Asia WGS

AF:

0.559

AC:

1946

AN:

3478

EpiCase

AF:

0.458

EpiControl

AF:

0.467

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

7.1

DANN

Benign

0.61

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over