NM_001377275.1:c.1957+534C>T

Variant names:

• chr1-7821174-C-T
• rs17374292
• NM_001377275.1:c.1957+534C>T

Variant summary

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

The NM_001377275.1(PER3):​c.1957+534C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,176 control chromosomes in the GnomAD database, including 1,817 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 0.14 (1817 hom., cov: 33)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 8 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 (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER3	NM_001377275.1	c.1957+534C>T		intron_variant	Intron 16 of 21	ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8	c.1957+534C>T		intron_variant	Intron 16 of 21	1	NM_001377275.1	ENSP00000366755.3

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21860 AN: 152058 Hom.: 1814 Cov.: 33

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.0918

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.0410

Gnomad SAS AF: 0.0432

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.144 AC: 21879 AN: 152176 Hom.: 1817 Cov.: 33 AF XY: 0.143 AC XY: 10668 AN XY: 74398

African (AFR) AF: 0.161 AC: 6667 AN: 41516

American (AMR) AF: 0.0917 AC: 1401 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0452 AC: 157 AN: 3472

East Asian (EAS) AF: 0.0413 AC: 214 AN: 5186

South Asian (SAS) AF: 0.0428 AC: 206 AN: 4812

European-Finnish (FIN) AF: 0.244 AC: 2578 AN: 10582

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10361 AN: 68008

Other (OTH) AF: 0.112 AC: 236 AN: 2110

Alfa AF: 0.0920 Hom.: 130

Bravo AF: 0.133

Asia WGS AF: 0.0650 AC: 227 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	0.45
DANN	Benign	0.60
PhyloP100		-1.2
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: rs17374292; hg19: chr1-7881234;