5-160253638-C-A

Variant names:

• chr5-160253638-C-A
• rs747988573
• NM_001308173.3:c.904G>T

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.904G>T​(p.Val302Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,230 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. V302M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCNJL NM_001308173.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.05
• Publications: 5 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=0.08674696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNJL	NM_001308173.3	c.904G>T	p.Val302Leu	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.904G>T	p.Val302Leu	missense_variant	Exon 6 of 6	2	NM_001308173.3	ENSP00000257536.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460230 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726194

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26032

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111102

Other (OTH) AF: 0.00 AC: 0 AN: 60308

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.0033	T;.;.;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	D;.;T;D
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.087	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.;.;.
PhyloP100		3.1
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.57	N;N;.;.
REVEL	Benign	0.036
Sift	Benign	0.31	T;T;.;.
Sift4G	Benign	0.80	T;T;.;T
Polyphen		0.40	B;B;B;.
Vest4		0.10
MutPred		0.22		Gain of disorder (P = 0.0585);.;.;.;
MVP		0.17
MPC		0.29
ClinPred		0.22	T
GERP RS		3.4
Varity_R		0.034
gMVP		0.24
Mutation Taster		=90/10	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

dbSNP: rs747988573; hg19: chr5-159680645;