rs757655932

Variant names:

• chr5-160253667-G-A
• rs757655932
• NM_001308173.3:c.875C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-160253667-G-A
• chr5-160253667-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001308173.3(CCNJL):​c.875C>T​(p.Ala292Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,608,642 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. 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. A292G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• 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: 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=0.060201377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNJL	NM_001308173.3	c.875C>T	p.Ala292Val	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>T	p.Ala292Val	missense_variant	Exon 6 of 6	2	NM_001308173.3	ENSP00000257536.7

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000245 AC: 6 AN: 245316 AF XY: 0.0000375

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000903

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.0000124 AC: 18 AN: 1456472 Hom.: 0 Cov.: 31 AF XY: 0.0000152 AC XY: 11 AN XY: 723622

African (AFR) AF: 0.0000599 AC: 2 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25922

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39542

South Asian (SAS) AF: 0.0000699 AC: 6 AN: 85856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000812 AC: 9 AN: 1108504

Other (OTH) AF: 0.00 AC: 0 AN: 60116

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74334

African (AFR) AF: 0.0000965 AC: 4 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000331 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1019C>T (p.A340V) alteration is located in exon 7 (coding exon 6) of the CCNJL gene. This alteration results from a C to T substitution at nucleotide position 1019, causing the alanine (A) at amino acid position 340 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	0.077
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.87
DEOGEN2	Benign	0.0019	T;.;.;.
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.93
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.54	T;.;T;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.060	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;.;.
PhyloP100		3.7
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.27	N;N;.;.
REVEL	Benign	0.072
Sift	Benign	0.28	T;T;.;.
Sift4G	Benign	0.57	T;T;.;T
Polyphen		0.0060	B;B;B;.
Vest4		0.026
MutPred		0.20		Loss of disorder (P = 0.0892);.;.;.;
MVP		0.12
MPC		0.25
ClinPred		0.015	T
GERP RS		3.2
Varity_R		0.014
gMVP		0.31
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: rs757655932; hg19: chr5-159680674;