Genetic Variant PER3:c.391-269T>C (chr1-7787776-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001377275.1(PER3):c.391-269T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 452,418 control chromosomes in the GnomAD database, including 84,717 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 0.56 ( 25571 hom., cov: 33)

Exomes 𝑓: 0.62 ( 59146 hom. )

Consequence

PER3
NM_001377275.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.502

Publications

20 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER3	NM_001377275.1 link	c.391-269T>C		intron_variant	Intron 4 of 21	ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8 link	c.391-269T>C		intron_variant	Intron 4 of 21	1	NM_001377275.1	ENSP00000366755.3		P56645-2

Frequencies

GnomAD3 genomes

AF:

0.565

AC:

85885

AN:

152056

Hom.:

25560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.370

Gnomad AMI

AF:

0.663

Gnomad AMR

AF:

0.698

Gnomad ASJ

AF:

0.691

Gnomad EAS

AF:

0.568

Gnomad SAS

AF:

0.644

Gnomad FIN

AF:

0.663

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.623

Gnomad OTH

AF:

0.604

GnomAD4 exome

AF:

0.623

AC:

187198

AN:

300244

Hom.:

59146

Cov.:

AF XY:

0.628

AC XY:

100470

AN XY:

159902

show subpopulations

African (AFR)

AF:

0.365

AC:

3300

AN:

9030

American (AMR)

AF:

0.723

AC:

9719

AN:

13438

Ashkenazi Jewish (ASJ)

AF:

0.682

AC:

6065

AN:

8898

East Asian (EAS)

AF:

0.565

AC:

10026

AN:

17742

South Asian (SAS)

AF:

0.653

AC:

26411

AN:

40438

European-Finnish (FIN)

AF:

0.646

AC:

9588

AN:

14844

Middle Eastern (MID)

AF:

0.709

AC:

888

AN:

1252

European-Non Finnish (NFE)

AF:

0.623

AC:

110642

AN:

177540

Other (OTH)

AF:

0.619

AC:

10559

AN:

17062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

3355

6711

10066

13422

16777

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

578

1156

1734

2312

2890

<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:

0.565

AC:

85926

AN:

152174

Hom.:

25571

Cov.:

AF XY:

0.572

AC XY:

42516

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.370

AC:

15342

AN:

41506

American (AMR)

AF:

0.698

AC:

10680

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.691

AC:

2398

AN:

3470

East Asian (EAS)

AF:

0.567

AC:

2929

AN:

5162

South Asian (SAS)

AF:

0.644

AC:

3107

AN:

4824

European-Finnish (FIN)

AF:

0.663

AC:

7031

AN:

10598

Middle Eastern (MID)

AF:

0.724

AC:

213

AN:

294

European-Non Finnish (NFE)

AF:

0.623

AC:

42340

AN:

68000

Other (OTH)

AF:

0.607

AC:

1284

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1859

3719

5578

7438

9297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<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:

0.524

Hom.:

2407

Bravo

AF:

0.559

Asia WGS

AF:

0.593

AC:

2062

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.36

(source)

DANN

Benign

0.58

PhyloP100

-0.50

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over