18-23136001-C-G

Variant names:

• chr18-23136001-C-G
• rs771528127
• NM_001100619.3:c.239C>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.239C>G​(p.Pro80Arg) 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. 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. P80L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CABLES1 NM_001100619.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255
• 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=0.07698342).

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.239C>G	p.Pro80Arg	missense	Exon 1 of 10	NP_001094089.1	Q8TDN4-1
	CABLES1	NM_001256438.1		c.-137+1331C>G		intron	N/A	NP_001243367.1	Q8TDN4-4
	CABLES1	NR_023359.2		n.88+1350C>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.239C>G	p.Pro80Arg	missense	Exon 1 of 10	ENSP00000256925.7	Q8TDN4-1
	CABLES1	ENST00000877774.1		c.239C>G	p.Pro80Arg	missense	Exon 1 of 9	ENSP00000547833.1
	CABLES1	ENST00000952329.1		c.239C>G	p.Pro80Arg	missense	Exon 1 of 9	ENSP00000622388.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.26
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	0.030	N
REVEL	Benign	0.022
Sift	Benign	0.055	T
Sift4G	Benign	0.48	T
Polyphen		0.19	B
Vest4		0.052
MutPred		0.33		Loss of catalytic residue at P79 (P = 0.0151)
MVP		0.51
MPC		1.5
ClinPred		0.13	T
GERP RS		-2.4
PromoterAI		0.030	Neutral
Varity_R		0.050
gMVP		0.10
Mutation Taster		=96/4	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: rs771528127; hg19: chr18-20715965;