dbSNP rs1053447706: CCNJL:p.Thr274Ala (chr5-160253722-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001308173.3(CCNJL):c.820A>G(p.Thr274Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,431,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. T274P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCNJL
NM_001308173.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.480

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029689252).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNJL	NM_001308173.3 link	c.820A>G	p.Thr274Ala	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.820A>G	p.Thr274Ala	missense_variant	Exon 6 of 6	2	NM_001308173.3	ENSP00000257536.7		B4DZA8

Frequencies

GnomAD3 genomes

AF:

0.00000664

AC:

AN:

150652

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1431216

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

708928

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33010

American (AMR)

AF:

0.00

AC:

AN:

42364

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24450

East Asian (EAS)

AF:

0.00

AC:

AN:

39282

South Asian (SAS)

AF:

0.00

AC:

AN:

82322

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5610

European-Non Finnish (NFE)

AF:

9.11e-7

AC:

AN:

1097678

Other (OTH)

AF:

0.00

AC:

AN:

59164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000664

AC:

AN:

150652

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73508

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40856

American (AMR)

AF:

0.00

AC:

AN:

15128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5092

South Asian (SAS)

AF:

0.00

AC:

AN:

4744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67642

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.34

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.00015

T;.;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.49

T;.;T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.030

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.92

N;.;.;.

PhyloP100

-0.48

PrimateAI

Benign

0.48

PROVEAN

Benign

0.20

N;N;.;.

REVEL

Benign

0.0090

Sift

Benign

0.79

T;T;.;.

Sift4G

Benign

0.82

T;T;.;T

Polyphen

0.0

B;B;B;.

Vest4

0.022

MutPred

0.42

Loss of glycosylation at T322 (P = 0.0016);.;.;.;

MVP

0.030

MPC

0.24

ClinPred

0.020

GERP RS

-1.3

Varity_R

0.020

gMVP

0.33

Mutation Taster

=97/3

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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rs1053447706

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over