Variant 1-7837073-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001377275.1(PER3):c.3473A>G(p.His1158Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,613,086 control chromosomes in the GnomAD database, including 28,349 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2131 hom., cov: 32)

Exomes 𝑓: 0.18 ( 26218 hom. )

Consequence

PER3
NM_001377275.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0170

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020701885).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PER3	NM_001377275.1 linkuse as main transcript	c.3473A>G	p.His1158Arg	missense_variant	21/22	ENST00000377532.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PER3	ENST00000377532.8 linkuse as main transcript	c.3473A>G	p.His1158Arg	missense_variant	21/22	1	NM_001377275.1	A2	P56645-2

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23881

AN:

152092

Hom.:

2130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0894

Gnomad AMI

AF:

0.114

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.0112

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.151

GnomAD3 exomes

AF:

0.169

AC:

42547

AN:

251126

Hom.:

4125

AF XY:

0.171

AC XY:

23175

AN XY:

135734

show subpopulations

Gnomad AFR exome

AF:

0.0906

Gnomad AMR exome

AF:

0.193

Gnomad ASJ exome

AF:

0.144

Gnomad EAS exome

AF:

0.00419

Gnomad SAS exome

AF:

0.177

Gnomad FIN exome

AF:

0.245

Gnomad NFE exome

AF:

0.186

Gnomad OTH exome

AF:

0.176

GnomAD4 exome

AF:

0.185

AC:

270122

AN:

1460876

Hom.:

26218

Cov.:

AF XY:

0.184

AC XY:

134045

AN XY:

726730

show subpopulations

Gnomad4 AFR exome

AF:

0.0875

Gnomad4 AMR exome

AF:

0.194

Gnomad4 ASJ exome

AF:

0.146

Gnomad4 EAS exome

AF:

0.0192

Gnomad4 SAS exome

AF:

0.175

Gnomad4 FIN exome

AF:

0.241

Gnomad4 NFE exome

AF:

0.194

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.157

AC:

23911

AN:

152210

Hom.:

2131

Cov.:

AF XY:

0.159

AC XY:

11856

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0896

Gnomad4 AMR

AF:

0.190

Gnomad4 ASJ

AF:

0.156

Gnomad4 EAS

AF:

0.0112

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.240

Gnomad4 NFE

AF:

0.189

Gnomad4 OTH

AF:

0.150

Alfa

AF:

0.176

Hom.:

6277

Bravo

AF:

0.148

TwinsUK

AF:

0.192

AC:

713

ALSPAC

AF:

0.212

AC:

817

ESP6500AA

AF:

0.0960

AC:

423

ESP6500EA

AF:

0.191

AC:

1644

ExAC

AF:

0.166

AC:

20132

Asia WGS

AF:

0.0710

AC:

245

AN:

3478

EpiCase

AF:

0.184

EpiControl

AF:

0.184

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.19

DANN

Benign

0.73

DEOGEN2

Benign

0.017

.;T;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.47

T;T;.;T

MetaRNN

Benign

0.0021

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

.;.;.;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.76

.;.;N;N

REVEL

Benign

0.019

Sift

Benign

0.25

.;.;T;T

Sift4G

Benign

0.32

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.052

MPC

0.11

ClinPred

0.0026

GERP RS

-8.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.037

gMVP

0.048

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