Variant 5-160259529-G-A 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_001308173.3(CCNJL):c.523C>T(p.Arg175Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000424 in 1,614,162 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 1 hom. )

Consequence

CCNJL
NM_001308173.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99

Variant links:

Genes affected

CCNJL (HGNC:25876): (cyclin J like) Predicted to enable cyclin-dependent protein serine/threonine kinase regulator activity. Predicted to be involved in mitotic cell cycle phase transition and regulation of cyclin-dependent protein serine/threonine kinase activity. Predicted to be part of cyclin-dependent protein kinase holoenzyme complex. Predicted to be active in centrosome; cytoplasm; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CCNJL 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=0.019306064).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNJL	NM_001308173.3 linkuse as main transcript	c.523C>T	p.Arg175Cys	missense_variant	4/6	ENST00000257536.13	NP_001295102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNJL	ENST00000257536.13 linkuse as main transcript	c.523C>T	p.Arg175Cys	missense_variant	4/6	2	NM_001308173.3	ENSP00000257536	P1

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000989

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000574

AC:

143

AN:

249094

Hom.:

AF XY:

0.000511

AC XY:

AN XY:

135154

show subpopulations

Gnomad AFR exome

AF:

0.000839

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00130

Gnomad NFE exome

AF:

0.000851

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000414

AC:

605

AN:

1461842

Hom.:

Cov.:

AF XY:

0.000393

AC XY:

286

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000992

Gnomad4 NFE exome

AF:

0.000447

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.000525

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000409

Hom.:

Bravo

AF:

0.000487

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000239

AC:

ESP6500EA

AF:

0.000712

AC:

ExAC

AF:

0.000727

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000711

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

Aug 17, 2021

The c.667C>T (p.R223C) alteration is located in exon 5 (coding exon 4) of the CCNJL gene. This alteration results from a C to T substitution at nucleotide position 667, causing the arginine (R) at amino acid position 223 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

0.10

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.47

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0069

T;.;.;.;.

Eigen

Benign

0.14

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.91

D;.;D;D;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.019

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.55

N;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.9

N;N;.;.;N

REVEL

Benign

0.10

Sift

Uncertain

0.014

D;D;.;.;D

Sift4G

Uncertain

0.034

D;D;.;D;D

Polyphen

1.0

D;D;D;.;D

Vest4

0.39

MVP

0.62

MPC

0.93

ClinPred

0.038

GERP RS

2.3

Varity_R

0.073

gMVP

0.39

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