1-7784929-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001377275.1(PER3):c.52G>T(p.Ala18Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,539,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 0 hom. )

Consequence

PER3
NM_001377275.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.02

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

advanced sleep phase syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PER3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044365525).

BP6

Variant 1-7784929-G-T is Benign according to our data. Variant chr1-7784929-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3041411.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 173 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377275.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PER3	NM_001377275.1	MANE Select	c.52G>T	p.Ala18Ser	missense	Exon 2 of 22	NP_001364204.1	P56645-2
PER3	NM_001289862.2		c.52G>T	p.Ala18Ser	missense	Exon 2 of 22	NP_001276791.1	P56645-2
PER3	NM_001438696.1		c.52G>T	p.Ala18Ser	missense	Exon 2 of 22	NP_001425625.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PER3	ENST00000377532.8	TSL:1 MANE Select	c.52G>T	p.Ala18Ser	missense	Exon 2 of 22	ENSP00000366755.3	P56645-2
PER3	ENST00000361923.2	TSL:1	c.52G>T	p.Ala18Ser	missense	Exon 1 of 21	ENSP00000355031.2	P56645-1
PER3	ENST00000614998.4	TSL:1	c.52G>T	p.Ala18Ser	missense	Exon 2 of 23	ENSP00000479223.1	A0A087WV69

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

173

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.0209

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00197

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00104

AC:

183

AN:

176126

AF XY:

0.00100

show subpopulations

Gnomad AFR exome

AF:

0.000183

Gnomad AMR exome

AF:

0.000243

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000149

Gnomad NFE exome

AF:

0.00198

Gnomad OTH exome

AF:

0.00104

GnomAD4 exome

AF:

0.00144

AC:

1996

AN:

1387304

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

990

AN XY:

689200

show subpopulations

African (AFR)

AF:

0.000254

AC:

AN:

27532

American (AMR)

AF:

0.000115

AC:

AN:

25976

Ashkenazi Jewish (ASJ)

AF:

0.0000859

AC:

AN:

23288

East Asian (EAS)

AF:

0.00

AC:

AN:

34360

South Asian (SAS)

AF:

0.0000403

AC:

AN:

74532

European-Finnish (FIN)

AF:

0.000135

AC:

AN:

51998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5516

European-Non Finnish (NFE)

AF:

0.00175

AC:

1901

AN:

1087010

Other (OTH)

AF:

0.00128

AC:

AN:

57092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

104

209

313

418

522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00114

AC:

173

AN:

152326

Hom.:

Cov.:

AF XY:

0.000900

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41580

American (AMR)

AF:

0.000196

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00197

AC:

134

AN:

68030

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00149

Hom.:

Bravo

AF:

0.00110

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.00112

AC:

136

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

PER3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.6

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.013

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.47

M_CAP

Benign

0.0022

MetaRNN

Benign

0.0044

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.14

PhyloP100

1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.53

REVEL

Benign

0.055

Sift

Benign

0.36

Sift4G

Benign

0.72

Polyphen

0.87

Vest4

0.17

MVP

0.32

MPC

0.32

ClinPred

0.013

GERP RS

-1.1

PromoterAI

-0.058

Neutral

(source)

Varity_R

0.095

gMVP

0.099

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over