1-7785422-A-AT

Position:

• chr1-7785422-A-AT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_001377275.1(PER3):​c.129-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,578,936 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.00057 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (1 hom.)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.347

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 1-7785422-A-AT is Benign according to our data. Variant chr1-7785422-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 3034361.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 86 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER3	NM_001377275.1	c.129-10dupT		intron_variant		ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8	c.129-10dupT		intron_variant		1	NM_001377275.1	ENSP00000366755.3

Frequencies

GnomAD3 genomes AF: 0.000567 AC: 86 AN: 151658 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.000190

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000987

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.00124 AC: 1772 AN: 1427164 Hom.: 1 Cov.: 28 AF XY: 0.00118 AC XY: 837 AN XY: 710952

Gnomad4 AFR exome AF: 0.000430

Gnomad4 AMR exome AF: 0.0000688

Gnomad4 ASJ exome AF: 0.000157

Gnomad4 EAS exome AF: 0.000128

Gnomad4 SAS exome AF: 0.000320

Gnomad4 FIN exome AF: 0.0000755

Gnomad4 NFE exome AF: 0.00154

Gnomad4 OTH exome AF: 0.000678

GnomAD4 genome AF: 0.000567 AC: 86 AN: 151772 Hom.: 0 Cov.: 32 AF XY: 0.000580 AC XY: 43 AN XY: 74154

Gnomad4 AFR AF: 0.000266

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000417

Gnomad4 FIN AF: 0.000190

Gnomad4 NFE AF: 0.000987

Gnomad4 OTH AF: 0.00142

Bravo AF: 0.000567

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PER3-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 11, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		1.0

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

Other links and lift over

dbSNP: rs554573019; hg19: chr1-7845482;