Variant 17-8141884-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002616.3(PER1):c.3521C>G(p.Ser1174Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

PER1
NM_002616.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.22

Variant links:

Genes affected

PER1 (HGNC:8845): (period circadian regulator 1) 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 may increase the risk of getting certain cancers. Alternative splicing has been observed in this gene; however, these variants have not been fully described. [provided by RefSeq, Jan 2014]

PER1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3867097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER1	NM_002616.3 linkuse as main transcript	c.3521C>G	p.Ser1174Cys	missense_variant	22/23	ENST00000317276.9	NP_002607.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PER1	ENST00000317276.9 linkuse as main transcript	c.3521C>G	p.Ser1174Cys	missense_variant	22/23	1	NM_002616.3	ENSP00000314420	P1	O15534-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2022

The c.3521C>G (p.S1174C) alteration is located in exon 22 (coding exon 21) of the PER1 gene. This alteration results from a C to G substitution at nucleotide position 3521, causing the serine (S) at amino acid position 1174 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Uncertain

0.075

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

T;T

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.39

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.4

N;.

REVEL

Benign

0.18

Sift

Uncertain

0.0010

D;.

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.61

MutPred

0.32

Loss of phosphorylation at S1174 (P = 0.0213);.;

MVP

0.25

MPC

0.60

ClinPred

0.95

GERP RS

5.7

Varity_R

0.31

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over