1-7809988-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001377275.1(PER3):ā€‹c.1338T>Cā€‹(p.Ser446=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.917 in 1,613,778 control chromosomes in the GnomAD database, including 681,373 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: š‘“ 0.92 ( 64581 hom., cov: 32)
Exomes š‘“: 0.92 ( 616792 hom. )

Consequence

PER3
NM_001377275.1 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.441
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP7
Synonymous conserved (PhyloP=-0.441 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PER3NM_001377275.1 linkuse as main transcriptc.1338T>C p.Ser446= synonymous_variant 12/22 ENST00000377532.8
LOC124903833XR_007065450.1 linkuse as main transcriptn.1689A>G non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PER3ENST00000377532.8 linkuse as main transcriptc.1338T>C p.Ser446= synonymous_variant 12/221 NM_001377275.1 A2P56645-2

Frequencies

GnomAD3 genomes
AF:
0.918
AC:
139666
AN:
152162
Hom.:
64532
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.964
Gnomad AMI
AF:
0.834
Gnomad AMR
AF:
0.782
Gnomad ASJ
AF:
0.946
Gnomad EAS
AF:
0.725
Gnomad SAS
AF:
0.937
Gnomad FIN
AF:
0.958
Gnomad MID
AF:
0.943
Gnomad NFE
AF:
0.927
Gnomad OTH
AF:
0.910
GnomAD3 exomes
AF:
0.880
AC:
221176
AN:
251212
Hom.:
99019
AF XY:
0.891
AC XY:
121057
AN XY:
135792
show subpopulations
Gnomad AFR exome
AF:
0.966
Gnomad AMR exome
AF:
0.651
Gnomad ASJ exome
AF:
0.940
Gnomad EAS exome
AF:
0.715
Gnomad SAS exome
AF:
0.939
Gnomad FIN exome
AF:
0.957
Gnomad NFE exome
AF:
0.928
Gnomad OTH exome
AF:
0.900
GnomAD4 exome
AF:
0.917
AC:
1340096
AN:
1461498
Hom.:
616792
Cov.:
44
AF XY:
0.919
AC XY:
667917
AN XY:
727098
show subpopulations
Gnomad4 AFR exome
AF:
0.968
Gnomad4 AMR exome
AF:
0.668
Gnomad4 ASJ exome
AF:
0.941
Gnomad4 EAS exome
AF:
0.763
Gnomad4 SAS exome
AF:
0.937
Gnomad4 FIN exome
AF:
0.952
Gnomad4 NFE exome
AF:
0.927
Gnomad4 OTH exome
AF:
0.910
GnomAD4 genome
AF:
0.918
AC:
139771
AN:
152280
Hom.:
64581
Cov.:
32
AF XY:
0.915
AC XY:
68136
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.964
Gnomad4 AMR
AF:
0.781
Gnomad4 ASJ
AF:
0.946
Gnomad4 EAS
AF:
0.725
Gnomad4 SAS
AF:
0.938
Gnomad4 FIN
AF:
0.958
Gnomad4 NFE
AF:
0.927
Gnomad4 OTH
AF:
0.910
Alfa
AF:
0.930
Hom.:
34912
Bravo
AF:
0.902
Asia WGS
AF:
0.819
AC:
2848
AN:
3478
EpiCase
AF:
0.924
EpiControl
AF:
0.926

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
CADD
Benign
0.29
DANN
Benign
0.35

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs228669; hg19: chr1-7870048; COSMIC: COSV62707152; COSMIC: COSV62707152; API