dbSNP rs776850524: CCNJL:p.Val253Phe (chr5-160253785-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001308173.3(CCNJL):c.757G>T(p.Val253Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000734 in 1,363,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V253I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

CCNJL
NM_001308173.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.70

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32707635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNJL	NM_001308173.3 link	c.757G>T	p.Val253Phe	missense_variant	Exon 6 of 6	ENST00000257536.13	NP_001295102.1	Q8IV13B4DZA8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNJL	ENST00000257536.13 link	c.757G>T	p.Val253Phe	missense_variant	Exon 6 of 6	2	NM_001308173.3	ENSP00000257536.7		B4DZA8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.34e-7

AC:

AN:

1363252

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

668118

show subpopulations

African (AFR)

AF:

0.0000322

AC:

AN:

31068

American (AMR)

AF:

0.00

AC:

AN:

33190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20606

East Asian (EAS)

AF:

0.00

AC:

AN:

38776

South Asian (SAS)

AF:

0.00

AC:

AN:

72466

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5344

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1068238

Other (OTH)

AF:

0.00

AC:

AN:

56594

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0034

T;.;.;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.77

T;.;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.33

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;.;.;.

PhyloP100

1.7

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.64

N;N;.;.

REVEL

Benign

0.13

Sift

Benign

0.065

T;D;.;.

Sift4G

Uncertain

0.058

T;T;.;T

Polyphen

0.86

P;D;D;.

Vest4

0.18

MutPred

0.72

Loss of helix (P = 0.0558);.;.;.;

MVP

0.43

MPC

0.82

ClinPred

0.86

GERP RS

3.0

Varity_R

0.074

gMVP

0.54

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over