Variant 14-77113709-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033426.3(CIPC):c.591G>T(p.Leu197Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,460,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

CIPC
NM_033426.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

Variant links:

Genes affected

CIPC (HGNC:20365): (CLOCK interacting pacemaker) Predicted to be involved in negative regulation of circadian rhythm and negative regulation of transcription, DNA-templated. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CIPC links:

ENSG00000259164 (HGNC:):

ENSG00000259164 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06044647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIPC	NM_033426.3 linkuse as main transcript	c.591G>T	p.Leu197Phe	missense_variant	4/4	ENST00000361786.7	NP_219494.2	Q9C0C6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIPC	ENST00000361786.7 linkuse as main transcript	c.591G>T	p.Leu197Phe	missense_variant	4/4	1	NM_033426.3	ENSP00000355319.2		Q9C0C6
ENSG00000259164	ENST00000557752.1 linkuse as main transcript	n.136+7865G>T		intron_variant		5		ENSP00000456507.1		H3BS24

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250258

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135278

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1460272

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726286

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000216

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Nov 08, 2022

The c.591G>T (p.L197F) alteration is located in exon 4 (coding exon 3) of the CIPC gene. This alteration results from a G to T substitution at nucleotide position 591, causing the leucine (L) at amino acid position 197 to be replaced by a phenylalanine (F). 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

0.063

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.69

M_CAP

Benign

0.011

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.8

REVEL

Benign

0.13

Sift

Benign

0.43

Sift4G

Benign

0.22

Polyphen

0.13

Vest4

0.056

MutPred

0.32

Gain of glycosylation at S198 (P = 0.1078);

MVP

0.26

MPC

0.36

ClinPred

0.21

GERP RS

4.6

Varity_R

0.042

gMVP

0.24

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

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