rs2640908

Variant names:

• chr1-7829881-C-T
• rs2640908
• NM_001377275.1:c.2934C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001377275.1(PER3):​c.2934C>T​(p.Thr978Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,609,316 control chromosomes in the GnomAD database, including 36,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. T978T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.22 (4342 hom., cov: 31)
  • Exomes 𝑓: 0.20 (31701 hom.)
• Consequence: PER3 NM_001377275.1 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.367
• Publications: 43 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-7829881-C-T is Benign according to our data. Variant chr1-7829881-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060144.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.367 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER3	NM_001377275.1	MANE Select	c.2934C>T	p.Thr978Thr	synonymous	Exon 19 of 22	NP_001364204.1	P56645-2
	PER3	NM_001289862.2		c.2934C>T	p.Thr978Thr	synonymous	Exon 19 of 22	NP_001276791.1	P56645-2
	PER3	NM_001438696.1		c.2931C>T	p.Thr977Thr	synonymous	Exon 19 of 22	NP_001425625.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER3	ENST00000377532.8	TSL:1 MANE Select	c.2934C>T	p.Thr978Thr	synonymous	Exon 19 of 22	ENSP00000366755.3	P56645-2
	PER3	ENST00000361923.2	TSL:1	c.2907C>T	p.Thr969Thr	synonymous	Exon 18 of 21	ENSP00000355031.2	P56645-1
	PER3	ENST00000614998.4	TSL:1	c.2931C>T	p.Thr977Thr	synonymous	Exon 19 of 23	ENSP00000479223.1	A0A087WV69

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33612 AN: 151832 Hom.: 4343 Cov.: 31

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.0811

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.218

GnomAD2 exomes AF: 0.218 AC: 54510 AN: 250128 AF XY: 0.219

Gnomad AFR exome AF: 0.300

Gnomad AMR exome AF: 0.170

Gnomad ASJ exome AF: 0.242

Gnomad EAS exome AF: 0.493

Gnomad FIN exome AF: 0.0903

Gnomad NFE exome AF: 0.181

Gnomad OTH exome AF: 0.207

GnomAD4 exome AF: 0.196 AC: 286196 AN: 1457366 Hom.: 31701 Cov.: 35 AF XY: 0.198 AC XY: 143836 AN XY: 725186

African (AFR) AF: 0.311 AC: 10367 AN: 33376

American (AMR) AF: 0.171 AC: 7626 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 6342 AN: 26094

East Asian (EAS) AF: 0.489 AC: 19361 AN: 39628

South Asian (SAS) AF: 0.288 AC: 24772 AN: 86114

European-Finnish (FIN) AF: 0.0920 AC: 4916 AN: 53414

Middle Eastern (MID) AF: 0.242 AC: 1392 AN: 5760

European-Non Finnish (NFE) AF: 0.179 AC: 198076 AN: 1108086

Other (OTH) AF: 0.222 AC: 13344 AN: 60204

GnomAD4 genome AF: 0.221 AC: 33637 AN: 151950 Hom.: 4342 Cov.: 31 AF XY: 0.217 AC XY: 16086 AN XY: 74270

African (AFR) AF: 0.305 AC: 12612 AN: 41384

American (AMR) AF: 0.165 AC: 2514 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 828 AN: 3472

East Asian (EAS) AF: 0.473 AC: 2432 AN: 5142

South Asian (SAS) AF: 0.297 AC: 1429 AN: 4816

European-Finnish (FIN) AF: 0.0811 AC: 860 AN: 10604

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12289 AN: 67956

Other (OTH) AF: 0.217 AC: 457 AN: 2108

Alfa AF: 0.196 Hom.: 5748

Bravo AF: 0.231

Asia WGS AF: 0.342 AC: 1187 AN: 3476

EpiCase AF: 0.186

EpiControl AF: 0.191

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PER3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.7
DANN	Benign	0.50
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2640908; hg19: chr1-7889941; COSMIC: COSV62706060; COSMIC: COSV62706060;