NM_001377275.1:c.593-1900C>G

Variant names:

• chr1-7792057-C-G
• rs170631
• NM_001377275.1:c.593-1900C>G

Variant summary

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

Score: -12 - Benign

-12

BP4_StrongBA1

The NM_001377275.1(PER3):​c.593-1900C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.074 in 152,260 control chromosomes in the GnomAD database, including 522 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 0.074 (522 hom., cov: 32)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0997 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER3	NM_001377275.1	c.593-1900C>G		intron_variant	Intron 5 of 21	ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8	c.593-1900C>G		intron_variant	Intron 5 of 21	1	NM_001377275.1	ENSP00000366755.3

Frequencies

GnomAD3 genomes AF: 0.0740 AC: 11263 AN: 152142 Hom.: 521 Cov.: 32

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0695

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.0466

Gnomad SAS AF: 0.0887

Gnomad FIN AF: 0.0738

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0851

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

GnomAD4 genome AF: 0.0740 AC: 11263 AN: 152260 Hom.: 522 Cov.: 32 AF XY: 0.0727 AC XY: 5410 AN XY: 74444

African (AFR) AF: 0.0245 AC: 1018 AN: 41566

American (AMR) AF: 0.0694 AC: 1062 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 493 AN: 3470

East Asian (EAS) AF: 0.0465 AC: 241 AN: 5182

South Asian (SAS) AF: 0.0886 AC: 427 AN: 4820

European-Finnish (FIN) AF: 0.0738 AC: 782 AN: 10596

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6918 AN: 68012

Other (OTH) AF: 0.0842 AC: 178 AN: 2114

Alfa AF: 0.0824 Hom.: 73

Bravo AF: 0.0726

Asia WGS AF: 0.0630 AC: 217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.68
PhyloP100		-0.64
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: rs170631; hg19: chr1-7852117;