chr5-160253667-G-C

Variant names:

• chr5-160253667-G-C
• NM_001308173.3:c.875C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001308173.3(CCNJL):​c.875C>G​(p.Ala292Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A292V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCNJL NM_001308173.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.67
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07960075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNJL	NM_001308173.3	c.875C>G	p.Ala292Gly	missense_variant	Exon 6 of 6	ENST00000257536.13	NP_001295102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNJL	ENST00000257536.13	c.875C>G	p.Ala292Gly	missense_variant	Exon 6 of 6	2	NM_001308173.3	ENSP00000257536.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1019C>G (p.A340G) alteration is located in exon 7 (coding exon 6) of the CCNJL gene. This alteration results from a C to G substitution at nucleotide position 1019, causing the alanine (A) at amino acid position 340 to be replaced by a glycine (G). 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	0.081
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.74
DEOGEN2	Benign	0.0019	T;.;.;.
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.88
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.64	T;.;T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.080	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;.;.
PhyloP100		3.7
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.35	N;N;.;.
REVEL	Benign	0.070
Sift	Benign	0.22	T;T;.;.
Sift4G	Benign	0.78	T;T;.;T
Polyphen		0.14	B;B;B;.
Vest4		0.089
MutPred		0.14		Loss of glycosylation at T341 (P = 0.1312);.;.;.;
MVP		0.14
MPC		0.27
ClinPred		0.26	T
GERP RS		3.2
Varity_R		0.018
gMVP		0.27
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

hg19: chr5-159680674;