Variant 1-7827188-G-A 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.2259G>A(p.Pro753Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,610,900 control chromosomes in the GnomAD database, including 127,151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.43 ( 14670 hom., cov: 32)

Exomes 𝑓: 0.38 ( 112481 hom. )

Consequence

PER3
NM_001377275.1 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.16

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:

ENSG00000236266 (HGNC:):

ENSG00000236266 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-7827188-G-A is Benign according to our data. Variant chr1-7827188-G-A is described in ClinVar as [Benign]. Clinvar id is 3060684.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-3.16 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER3	NM_001377275.1 link	c.2259G>A	p.Pro753Pro	synonymous_variant	Exon 18 of 22	ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8 link	c.2259G>A	p.Pro753Pro	synonymous_variant	Exon 18 of 22	1	NM_001377275.1	ENSP00000366755.3		P56645-2

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64596

AN:

151852

Hom.:

14662

Cov.:

show subpopulations

Gnomad AFR

AF:

0.517

Gnomad AMI

AF:

0.276

Gnomad AMR

AF:

0.450

Gnomad ASJ

AF:

0.314

Gnomad EAS

AF:

0.788

Gnomad SAS

AF:

0.383

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.274

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.397

GnomAD3 exomes

AF:

0.430

AC:

105731

AN:

245866

Hom.:

25188

AF XY:

0.416

AC XY:

55698

AN XY:

133738

show subpopulations

Gnomad AFR exome

AF:

0.519

Gnomad AMR exome

AF:

0.565

Gnomad ASJ exome

AF:

0.320

Gnomad EAS exome

AF:

0.811

Gnomad SAS exome

AF:

0.365

Gnomad FIN exome

AF:

0.344

Gnomad NFE exome

AF:

0.360

Gnomad OTH exome

AF:

0.388

GnomAD4 exome

AF:

0.384

AC:

560026

AN:

1458930

Hom.:

112481

Cov.:

AF XY:

0.380

AC XY:

275859

AN XY:

725436

show subpopulations

Gnomad4 AFR exome

AF:

0.521

Gnomad4 AMR exome

AF:

0.552

Gnomad4 ASJ exome

AF:

0.323

Gnomad4 EAS exome

AF:

0.759

Gnomad4 SAS exome

AF:

0.370

Gnomad4 FIN exome

AF:

0.349

Gnomad4 NFE exome

AF:

0.363

Gnomad4 OTH exome

AF:

0.400

GnomAD4 genome

AF:

0.425

AC:

64652

AN:

151970

Hom.:

14670

Cov.:

AF XY:

0.424

AC XY:

31477

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.517

Gnomad4 AMR

AF:

0.450

Gnomad4 ASJ

AF:

0.314

Gnomad4 EAS

AF:

0.788

Gnomad4 SAS

AF:

0.382

Gnomad4 FIN

AF:

0.334

Gnomad4 NFE

AF:

0.363

Gnomad4 OTH

AF:

0.395

Alfa

AF:

0.354

Hom.:

2860

Bravo

AF:

0.442

Asia WGS

AF:

0.576

AC:

2002

AN:

3478

EpiCase

AF:

0.353

EpiControl

AF:

0.355

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

-0.82

CADD

Benign

0.019

DANN

Benign

0.88

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