Variant rs35899625 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000377532.8(PER3):c.2510T>G(p.Leu837Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000471 in 1,614,188 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 1 hom. )

Consequence

PER3
ENST00000377532.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.289

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047951043).

BP6

Variant 1-7827439-T-G is Benign according to our data. Variant chr1-7827439-T-G is described in ClinVar as [Benign]. Clinvar id is 741381.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 393 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER3	NM_001377275.1 linkuse as main transcript	c.2510T>G	p.Leu837Trp	missense_variant	18/22	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.2510T>G	p.Leu837Trp	missense_variant	18/22	1	NM_001377275.1	ENSP00000366755	A2	P56645-2
PER3	ENST00000361923.2 linkuse as main transcript	c.2486T>G	p.Leu829Trp	missense_variant	17/21	1		ENSP00000355031	P2	P56645-1
PER3	ENST00000614998.4 linkuse as main transcript	c.2510T>G	p.Leu837Trp	missense_variant	18/23	1		ENSP00000479223	A2
PER3	ENST00000613533.4 linkuse as main transcript	c.2510T>G	p.Leu837Trp	missense_variant	18/22	5		ENSP00000482093	A2	P56645-2

Frequencies

GnomAD3 genomes

AF:

0.00257

AC:

392

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00904

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000620

AC:

156

AN:

251462

Hom.:

AF XY:

0.000375

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00886

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000252

AC:

368

AN:

1461828

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

146

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00926

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000546

GnomAD4 genome

AF:

0.00258

AC:

393

AN:

152360

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

199

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00904

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000491

Hom.:

Bravo

AF:

0.00294

ESP6500AA

AF:

0.0104

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000708

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.035

.;T;.;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.30

T;T;.;T

MetaRNN

Benign

0.0048

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.2

.;.;.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.0

.;.;N;N

REVEL

Benign

0.13

Sift

Benign

0.043

.;.;D;D

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.99

D;.;D;D

Vest4

0.18

MVP

0.68

MPC

0.17

ClinPred

0.019

GERP RS

-1.6

Varity_R

0.032

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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