Variant 12-56418153-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000553532.6(TIMELESS):c.3435G>A(p.Ala1145=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00556 in 1,614,200 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0057 ( 27 hom. )

Consequence

TIMELESS
ENST00000553532.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.20

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 12-56418153-C-T is Benign according to our data. Variant chr12-56418153-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 786421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.2 with no splicing effect.

BS2

High AC in GnomAd4 at 648 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TIMELESS	NM_003920.5 linkuse as main transcript	c.3435G>A	p.Ala1145=	synonymous_variant	27/29	ENST00000553532.6	NP_003911.2
TIMELESS	NM_001330295.2 linkuse as main transcript	c.3432G>A	p.Ala1144=	synonymous_variant	27/29		NP_001317224.1
TIMELESS	NR_138471.2 linkuse as main transcript	n.3572G>A		non_coding_transcript_exon_variant	27/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMELESS	ENST00000553532.6 linkuse as main transcript	c.3435G>A	p.Ala1145=	synonymous_variant	27/29	1	NM_003920.5	ENSP00000450607	P4	Q9UNS1-1
TIMELESS	ENST00000229201.4 linkuse as main transcript	c.3432G>A	p.Ala1144=	synonymous_variant	27/29	5		ENSP00000229201	A2	Q9UNS1-2
TIMELESS	ENST00000557589.1 linkuse as main transcript	n.2003G>A		non_coding_transcript_exon_variant	11/13	2

Frequencies

GnomAD3 genomes

AF:

0.00425

AC:

647

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00885

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00563

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00397

AC:

998

AN:

251446

Hom.:

AF XY:

0.00404

AC XY:

549

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000849

Gnomad FIN exome

AF:

0.00906

Gnomad NFE exome

AF:

0.00571

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00569

AC:

8319

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00547

AC XY:

3976

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00262

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000661

Gnomad4 FIN exome

AF:

0.00781

Gnomad4 NFE exome

AF:

0.00664

Gnomad4 OTH exome

AF:

0.00495

GnomAD4 genome

AF:

0.00425

AC:

648

AN:

152318

Hom.:

Cov.:

AF XY:

0.00473

AC XY:

352

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.00627

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00885

Gnomad4 NFE

AF:

0.00563

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00482

Hom.:

Bravo

AF:

0.00383

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00583

EpiControl

AF:

0.00569

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2022	TIMELESS: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.57

DANN

Benign

0.36

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over