5-160253749-A-C

Position:

• chr5-160253749-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001308173.3(CCNJL):​c.793T>G​(p.Leu265Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: CCNJL NM_001308173.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.129

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11679202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNJL	NM_001308173.3	c.793T>G	p.Leu265Val	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	c.793T>G	p.Leu265Val	missense_variant	6/6	2	NM_001308173.3	ENSP00000257536	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.937T>G (p.L313V) alteration is located in exon 7 (coding exon 6) of the CCNJL gene. This alteration results from a T to G substitution at nucleotide position 937, causing the leucine (L) at amino acid position 313 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	0.080
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.9
DANN	Benign	0.90
DEOGEN2	Benign	0.0037	T;.;.;.
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.69	T;.;T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.40	N;N;.;.
REVEL	Benign	0.056
Sift	Benign	0.096	T;T;.;.
Sift4G	Benign	0.66	T;T;.;T
Polyphen		0.92	P;B;B;.
Vest4		0.086
MutPred		0.41		Loss of helix (P = 0.0444);.;.;.;
MVP		0.12
MPC		0.33
ClinPred		0.071	T
GERP RS		-2.2
Varity_R		0.039
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-159680756;