Variant rs2640908 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001377275.1(PER3):c.2934C>T(p.Thr978=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,609,316 control chromosomes in the GnomAD database, including 36,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.22 ( 4342 hom., cov: 31)

Exomes 𝑓: 0.20 ( 31701 hom. )

Consequence

PER3
NM_001377275.1 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.367

Variant links:

Genes affected

PER3 (HGNC:8847): (period circadian regulator 3) This gene is a member of the Period family of genes and is expressed in a circadian pattern in the suprachiasmatic nucleus, the primary circadian pacemaker in the mammalian brain. Genes in this family encode components of the circadian rhythms of locomotor activity, metabolism, and behavior. This gene is upregulated by CLOCK/ARNTL heterodimers but then represses this upregulation in a feedback loop using PER/CRY heterodimers to interact with CLOCK/ARNTL. Polymorphisms in this gene have been linked to sleep disorders. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2014]

PER3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 1-7829881-C-T is Benign according to our data. Variant chr1-7829881-C-T is described in ClinVar as [Benign]. Clinvar id is 3060144.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.367 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER3	NM_001377275.1 linkuse as main transcript	c.2934C>T	p.Thr978=	synonymous_variant	19/22	ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8 linkuse as main transcript	c.2934C>T	p.Thr978=	synonymous_variant	19/22	1	NM_001377275.1	ENSP00000366755	A2	P56645-2
PER3	ENST00000361923.2 linkuse as main transcript	c.2907C>T	p.Thr969=	synonymous_variant	18/21	1		ENSP00000355031	P2	P56645-1
PER3	ENST00000614998.4 linkuse as main transcript	c.2931C>T	p.Thr977=	synonymous_variant	19/23	1		ENSP00000479223	A2
PER3	ENST00000613533.4 linkuse as main transcript	c.2934C>T	p.Thr978=	synonymous_variant	19/22	5		ENSP00000482093	A2	P56645-2

Frequencies

GnomAD3 genomes

AF:

0.221

AC:

33612

AN:

151832

Hom.:

4343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.473

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.0811

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.218

GnomAD3 exomes

AF:

0.218

AC:

54510

AN:

250128

Hom.:

7245

AF XY:

0.219

AC XY:

29674

AN XY:

135316

show subpopulations

Gnomad AFR exome

AF:

0.300

Gnomad AMR exome

AF:

0.170

Gnomad ASJ exome

AF:

0.242

Gnomad EAS exome

AF:

0.493

Gnomad SAS exome

AF:

0.287

Gnomad FIN exome

AF:

0.0903

Gnomad NFE exome

AF:

0.181

Gnomad OTH exome

AF:

0.207

GnomAD4 exome

AF:

0.196

AC:

286196

AN:

1457366

Hom.:

31701

Cov.:

AF XY:

0.198

AC XY:

143836

AN XY:

725186

show subpopulations

Gnomad4 AFR exome

AF:

0.311

Gnomad4 AMR exome

AF:

0.171

Gnomad4 ASJ exome

AF:

0.243

Gnomad4 EAS exome

AF:

0.489

Gnomad4 SAS exome

AF:

0.288

Gnomad4 FIN exome

AF:

0.0920

Gnomad4 NFE exome

AF:

0.179

Gnomad4 OTH exome

AF:

0.222

GnomAD4 genome

AF:

0.221

AC:

33637

AN:

151950

Hom.:

4342

Cov.:

AF XY:

0.217

AC XY:

16086

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.305

Gnomad4 AMR

AF:

0.165

Gnomad4 ASJ

AF:

0.238

Gnomad4 EAS

AF:

0.473

Gnomad4 SAS

AF:

0.297

Gnomad4 FIN

AF:

0.0811

Gnomad4 NFE

AF:

0.181

Gnomad4 OTH

AF:

0.217

Alfa

AF:

0.194

Hom.:

4096

Bravo

AF:

0.231

Asia WGS

AF:

0.342

AC:

1187

AN:

3476

EpiCase

AF:

0.186

EpiControl

AF:

0.191

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PER3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.7

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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