Genetic Variant PER3:c.1658+147C>G (chr1-7819567-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001377275.1(PER3):c.1658+147C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 688,198 control chromosomes in the GnomAD database, including 15 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 0.0030 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 13 hom. )

Consequence

PER3
NM_001377275.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14

Publications

26 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:

ENSG00000236266 (HGNC:):

ENSG00000236266 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BS2

High AC in GnomAd4 at 456 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	Effect	Exon Rank	Protein	UniProt
PER3	NM_001377275.1	MANE Select	c.1658+147C>G	intron	N/A	NP_001364204.1	P56645-2
PER3	NM_001289862.2		c.1658+147C>G	intron	N/A	NP_001276791.1	P56645-2
PER3	NM_001438696.1		c.1655+147C>G	intron	N/A	NP_001425625.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PER3	ENST00000377532.8	TSL:1 MANE Select	c.1658+147C>G	intron	N/A	ENSP00000366755.3	P56645-2
PER3	ENST00000361923.2	TSL:1	c.1634+147C>G	intron	N/A	ENSP00000355031.2	P56645-1
PER3	ENST00000614998.4	TSL:1	c.1658+147C>G	intron	N/A	ENSP00000479223.1	A0A087WV69

Frequencies

GnomAD3 genomes

AF:

0.00300

AC:

456

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0174

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00334

Gnomad OTH

AF:

0.00191

GnomAD4 exome

AF:

0.00334

AC:

1788

AN:

536048

Hom.:

AF XY:

0.00318

AC XY:

908

AN XY:

285402

show subpopulations

African (AFR)

AF:

0.000345

AC:

AN:

14478

American (AMR)

AF:

0.000121

AC:

AN:

24842

Ashkenazi Jewish (ASJ)

AF:

0.00786

AC:

114

AN:

14512

East Asian (EAS)

AF:

0.0000290

AC:

AN:

34442

South Asian (SAS)

AF:

0.000744

AC:

AN:

49742

European-Finnish (FIN)

AF:

0.0183

AC:

636

AN:

34790

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2190

European-Non Finnish (NFE)

AF:

0.00270

AC:

896

AN:

332072

Other (OTH)

AF:

0.00331

AC:

AN:

28980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

162

243

324

405

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.00300

AC:

456

AN:

152150

Hom.:

Cov.:

AF XY:

0.00360

AC XY:

268

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41498

American (AMR)

AF:

0.000458

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00691

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0174

AC:

184

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00334

AC:

227

AN:

68010

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000103

Hom.:

6698

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.21

(source)

DANN

Benign

0.44

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

Other links and lift over