rs10864316

Variant names:

• chr1-7812016-A-G
• rs10864316
• NM_001377275.1:c.1522+1428A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377275.1(PER3):​c.1522+1428A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,140 control chromosomes in the GnomAD database, including 2,122 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 0.16 (2122 hom., cov: 32)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.985
• Publications: 16 publications found

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

ENSG00000236266 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER3	NM_001377275.1	c.1522+1428A>G		intron_variant	Intron 13 of 21	ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8	c.1522+1428A>G		intron_variant	Intron 13 of 21	1	NM_001377275.1	ENSP00000366755.3

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23830 AN: 152022 Hom.: 2121 Cov.: 32

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.157 AC: 23861 AN: 152140 Hom.: 2122 Cov.: 32 AF XY: 0.159 AC XY: 11829 AN XY: 74362

African (AFR) AF: 0.0896 AC: 3722 AN: 41522

American (AMR) AF: 0.188 AC: 2878 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 541 AN: 3470

East Asian (EAS) AF: 0.0108 AC: 56 AN: 5180

South Asian (SAS) AF: 0.173 AC: 835 AN: 4824

European-Finnish (FIN) AF: 0.240 AC: 2535 AN: 10554

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12846 AN: 67990

Other (OTH) AF: 0.151 AC: 319 AN: 2114

Alfa AF: 0.182 Hom.: 1373

Bravo AF: 0.147

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.098
DANN	Benign	0.71
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10864316; hg19: chr1-7872076;