chr18-23135917-C-G

Variant names:

• chr18-23135917-C-G
• rs1453539997
• NM_001100619.3:c.155C>G

Variant summary

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

The NM_001100619.3(CABLES1):​c.155C>G​(p.Pro52Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000845 in 946,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. P52S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000085 (0 hom.)
• Consequence: CABLES1 NM_001100619.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.953
• Publications: 0 publications found

Genes affected

CABLES1 (HGNC:25097): (Cdk5 and Abl enzyme substrate 1) This gene encodes a protein involved in regulation of the cell cycle through interactions with several cyclin-dependent kinases. One study (PMID: 16177568) reported aberrant splicing of transcripts from this gene which results in removal of the cyclin binding domain only in human cancer cells, and reduction in gene expression was shown in colorectal cancers (PMID: 17982127).Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

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=0.1468345).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100619.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABLES1	NM_001100619.3	MANE Select	c.155C>G	p.Pro52Arg	missense	Exon 1 of 10	NP_001094089.1	Q8TDN4-1
	CABLES1	NM_001256438.1		c.-137+1247C>G		intron	N/A	NP_001243367.1	Q8TDN4-4
	CABLES1	NR_023359.2		n.88+1266C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABLES1	ENST00000256925.12	TSL:1 MANE Select	c.155C>G	p.Pro52Arg	missense	Exon 1 of 10	ENSP00000256925.7	Q8TDN4-1
	CABLES1	ENST00000877774.1		c.155C>G	p.Pro52Arg	missense	Exon 1 of 9	ENSP00000547833.1
	CABLES1	ENST00000952329.1		c.155C>G	p.Pro52Arg	missense	Exon 1 of 9	ENSP00000622388.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000845 AC: 8 AN: 946576 Hom.: 0 Cov.: 30 AF XY: 0.00000888 AC XY: 4 AN XY: 450478

African (AFR) AF: 0.00 AC: 0 AN: 18526

American (AMR) AF: 0.00 AC: 0 AN: 4930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8214

East Asian (EAS) AF: 0.00 AC: 0 AN: 10780

South Asian (SAS) AF: 0.0000505 AC: 1 AN: 19808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2232

European-Non Finnish (NFE) AF: 0.00000835 AC: 7 AN: 838216

Other (OTH) AF: 0.00 AC: 0 AN: 33518

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.31	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.95
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.13	N
REVEL	Benign	0.042
Sift	Benign	0.062	T
Sift4G	Benign	0.11	T
Polyphen		0.49	P
Vest4		0.13
MutPred		0.19		Loss of glycosylation at P52 (P = 0.0042)
MVP		0.59
MPC		1.2
ClinPred		0.30	T
GERP RS		-0.053
PromoterAI		0.022	Neutral
Varity_R		0.040
gMVP		0.27
Mutation Taster		=88/12	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: rs1453539997; hg19: chr18-20715881;