1-7835906-C-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.3359C>T(p.Thr1120Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000696 in 1,611,220 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 6 hom. )

Consequence

PER3
NM_001377275.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.69

Publications

5 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=0.010260373).

BP6

Variant 1-7835906-C-T is Benign according to our data. Variant chr1-7835906-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3039488.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 103 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
PER3	NM_001377275.1	MANE Select	c.3359C>T	p.Thr1120Ile	missense	Exon 20 of 22	NP_001364204.1
PER3	NM_001289862.2		c.3359C>T	p.Thr1120Ile	missense	Exon 20 of 22	NP_001276791.1
PER3	NM_001438696.1		c.3356C>T	p.Thr1119Ile	missense	Exon 20 of 22	NP_001425625.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PER3	ENST00000377532.8	TSL:1 MANE Select	c.3359C>T	p.Thr1120Ile	missense	Exon 20 of 22	ENSP00000366755.3
PER3	ENST00000361923.2	TSL:1	c.3332C>T	p.Thr1111Ile	missense	Exon 19 of 21	ENSP00000355031.2
PER3	ENST00000614998.4	TSL:1	c.3302C>T	p.Thr1101Ile	missense	Exon 21 of 23	ENSP00000479223.1

Frequencies

GnomAD3 genomes

AF:

0.000670

AC:

102

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00113

AC:

283

AN:

251232

AF XY:

0.00119

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00151

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000827

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.000698

AC:

1018

AN:

1458886

Hom.:

Cov.:

AF XY:

0.000799

AC XY:

580

AN XY:

725970

show subpopulations

African (AFR)

AF:

0.000240

AC:

AN:

33402

American (AMR)

AF:

0.00177

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00168

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00330

AC:

284

AN:

86150

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00678

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.000427

AC:

474

AN:

1109348

Other (OTH)

AF:

0.00146

AC:

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

100

149

199

249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000676

AC:

103

AN:

152334

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41590

American (AMR)

AF:

0.00137

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00435

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000706

AC:

AN:

68026

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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:

0.000510

Hom.:

Bravo

AF:

0.000801

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00115

AC:

140

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00115

EpiControl

AF:

0.00142

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PER3-related disorder

Benign:1

May 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

8.0

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.29

Eigen

Benign

-0.0090

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.56

M_CAP

Benign

0.013

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PhyloP100

1.7

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.14

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0050

Polyphen

0.99

Vest4

0.34

MVP

0.43

MPC

0.091

ClinPred

0.066

GERP RS

3.1

Varity_R

0.25

gMVP

0.80

Mutation Taster

=97/3

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

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over