Genetic Variant PER3:c.645-2239T>C (chr1-7796286-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.645-2239T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 149,090 control chromosomes in the GnomAD database, including 9,838 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 0.35 ( 9838 hom., cov: 27)

Consequence

PER3
NM_001377275.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0110

Publications

28 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

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.645-2239T>C	intron	N/A	NP_001364204.1	P56645-2
PER3	NM_001289862.2		c.645-2239T>C	intron	N/A	NP_001276791.1	P56645-2
PER3	NM_001438696.1		c.642-2239T>C	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.645-2239T>C	intron	N/A	ENSP00000366755.3	P56645-2
PER3	ENST00000361923.2	TSL:1	c.642-2239T>C	intron	N/A	ENSP00000355031.2	P56645-1
PER3	ENST00000614998.4	TSL:1	c.645-2239T>C	intron	N/A	ENSP00000479223.1	A0A087WV69

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

52322

AN:

148996

Hom.:

9834

Cov.:

show subpopulations

Gnomad AFR

AF:

0.261

Gnomad AMI

AF:

0.498

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.504

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.424

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.613

Gnomad NFE

AF:

0.403

Gnomad OTH

AF:

0.392

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.351

AC:

52339

AN:

149090

Hom.:

9838

Cov.:

AF XY:

0.351

AC XY:

25391

AN XY:

72414

show subpopulations

African (AFR)

AF:

0.262

AC:

10597

AN:

40522

American (AMR)

AF:

0.313

AC:

4634

AN:

14818

Ashkenazi Jewish (ASJ)

AF:

0.504

AC:

1733

AN:

3438

East Asian (EAS)

AF:

0.198

AC:

1003

AN:

5062

South Asian (SAS)

AF:

0.424

AC:

2015

AN:

4752

European-Finnish (FIN)

AF:

0.380

AC:

3660

AN:

9636

Middle Eastern (MID)

AF:

0.614

AC:

178

AN:

290

European-Non Finnish (NFE)

AF:

0.403

AC:

27250

AN:

67598

Other (OTH)

AF:

0.396

AC:

820

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

1477

2954

4430

5907

7384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

518

1036

1554

2072

2590

<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:

0.403

Hom.:

19045

Bravo

AF:

0.343

Asia WGS

AF:

0.332

AC:

1155

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

5.3

(source)

DANN

Benign

0.66

PhyloP100

-0.011

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over