1-7784409-G-T

Variant names:

• chr1-7784409-G-T
• rs228730
• NM_001377275.1:c.-225+33G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016831.4(PER3):​c.-284G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000666 in 150,232 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PER3 NM_016831.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016831.4. 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.-225+33G>T		intron	N/A	NP_001364204.1	P56645-2
	PER3	NM_016831.4		c.-284G>T		5_prime_UTR	Exon 1 of 22	NP_058515.1	A2I2N5
	PER3	NM_001289861.2		c.-284G>T		5_prime_UTR	Exon 1 of 23	NP_001276790.1	A0A087WV69

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER3	ENST00000377532.8	TSL:1 MANE Select	c.-225+33G>T		intron	N/A	ENSP00000366755.3	P56645-2
	PER3	ENST00000377541.5	TSL:1	c.-225+33G>T		intron	N/A	ENSP00000366764.1	Q8TAR6
	PER3	ENST00000961537.1		c.-469G>T		5_prime_UTR	Exon 1 of 21	ENSP00000631596.1

Frequencies

GnomAD3 genomes AF: 0.00000666 AC: 1 AN: 150232 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000664

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 520 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 378

African (AFR) AF: 0.00 AC: 0 AN: 16

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.00 AC: 0 AN: 32

South Asian (SAS) AF: 0.00 AC: 0 AN: 40

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 398

Other (OTH) AF: 0.00 AC: 0 AN: 20

GnomAD4 genome AF: 0.00000666 AC: 1 AN: 150232 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73344

African (AFR) AF: 0.00 AC: 0 AN: 41202

American (AMR) AF: 0.0000664 AC: 1 AN: 15060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67204

Other (OTH) AF: 0.00 AC: 0 AN: 2044

Alfa AF: 0.00 Hom.: 18

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.57
PhyloP100		-0.37
PromoterAI		-0.065	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs228730; hg19: chr1-7844469;