Variant 5-160253743-T-C 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.799A>G(p.Met267Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000436 in 1,561,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

CCNJL
NM_001308173.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.571

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=0.058636367).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNJL	NM_001308173.3 linkuse as main transcript	c.799A>G	p.Met267Val	missense_variant	6/6	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.799A>G	p.Met267Val	missense_variant	6/6	2	NM_001308173.3	ENSP00000257536	P1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000491

AC:

AN:

203698

Hom.:

AF XY:

0.0000727

AC XY:

AN XY:

109988

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000733

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000461

AC:

AN:

1409054

Hom.:

Cov.:

AF XY:

0.0000518

AC XY:

AN XY:

695382

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.0000759

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000515

Gnomad4 OTH exome

AF:

0.0000343

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000497

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 07, 2023

The c.943A>G (p.M315V) alteration is located in exon 7 (coding exon 6) of the CCNJL gene. This alteration results from a A to G substitution at nucleotide position 943, causing the methionine (M) at amino acid position 315 to be replaced by a valine (V). 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

0.057

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.13

DANN

Benign

0.45

DEOGEN2

Benign

0.0014

T;.;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.60

T;.;T;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.059

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.58

N;N;.;.

REVEL

Benign

0.045

Sift

Benign

0.088

T;T;.;.

Sift4G

Benign

0.15

T;T;.;T

Polyphen

0.0050

B;B;B;.

Vest4

0.097

MutPred

0.55

Gain of loop (P = 0.0435);.;.;.;

MVP

0.12

MPC

0.25

ClinPred

0.044

GERP RS

-2.6

Varity_R

0.032

gMVP

0.31

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