Variant chr1-7809988-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001377275.1(PER3):c.1338T>C(p.Ser446=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.917 in 1,613,778 control chromosomes in the GnomAD database, including 681,373 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 0.92 ( 64581 hom., cov: 32)

Exomes 𝑓: 0.92 ( 616792 hom. )

Consequence

PER3
NM_001377275.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.441

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:

LOC124903833 (HGNC:):

LOC124903833 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP7

Synonymous conserved (PhyloP=-0.441 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 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.1338T>C	p.Ser446=	synonymous_variant	12/22	ENST00000377532.8
LOC124903833	XR_007065450.1 linkuse as main transcript	n.1689A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PER3	ENST00000377532.8 linkuse as main transcript	c.1338T>C	p.Ser446=	synonymous_variant	12/22	1	NM_001377275.1	A2	P56645-2

Frequencies

GnomAD3 genomes

AF:

0.918

AC:

139666

AN:

152162

Hom.:

64532

Cov.:

show subpopulations

Gnomad AFR

AF:

0.964

Gnomad AMI

AF:

0.834

Gnomad AMR

AF:

0.782

Gnomad ASJ

AF:

0.946

Gnomad EAS

AF:

0.725

Gnomad SAS

AF:

0.937

Gnomad FIN

AF:

0.958

Gnomad MID

AF:

0.943

Gnomad NFE

AF:

0.927

Gnomad OTH

AF:

0.910

GnomAD3 exomes

AF:

0.880

AC:

221176

AN:

251212

Hom.:

99019

AF XY:

0.891

AC XY:

121057

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.966

Gnomad AMR exome

AF:

0.651

Gnomad ASJ exome

AF:

0.940

Gnomad EAS exome

AF:

0.715

Gnomad SAS exome

AF:

0.939

Gnomad FIN exome

AF:

0.957

Gnomad NFE exome

AF:

0.928

Gnomad OTH exome

AF:

0.900

GnomAD4 exome

AF:

0.917

AC:

1340096

AN:

1461498

Hom.:

616792

Cov.:

AF XY:

0.919

AC XY:

667917

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.968

Gnomad4 AMR exome

AF:

0.668

Gnomad4 ASJ exome

AF:

0.941

Gnomad4 EAS exome

AF:

0.763

Gnomad4 SAS exome

AF:

0.937

Gnomad4 FIN exome

AF:

0.952

Gnomad4 NFE exome

AF:

0.927

Gnomad4 OTH exome

AF:

0.910

GnomAD4 genome

AF:

0.918

AC:

139771

AN:

152280

Hom.:

64581

Cov.:

AF XY:

0.915

AC XY:

68136

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.964

Gnomad4 AMR

AF:

0.781

Gnomad4 ASJ

AF:

0.946

Gnomad4 EAS

AF:

0.725

Gnomad4 SAS

AF:

0.938

Gnomad4 FIN

AF:

0.958

Gnomad4 NFE

AF:

0.927

Gnomad4 OTH

AF:

0.910

Alfa

AF:

0.930

Hom.:

34912

Bravo

AF:

0.902

Asia WGS

AF:

0.819

AC:

2848

AN:

3478

EpiCase

AF:

0.924

EpiControl

AF:

0.926

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.29

DANN

Benign

0.35

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