Genetic Variant CABLES1:p.Ala114Gly (chr18-23136103-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001100619.3(CABLES1):c.341C>G(p.Ala114Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000966 in 1,035,572 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. A114V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 9.7e-7 ( 0 hom. )

Consequence

CABLES1
NM_001100619.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.08

Publications

0 publications found

Variant links:

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]

CABLES1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.12775171).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CABLES1	NM_001100619.3	MANE Select	c.341C>G	p.Ala114Gly	missense	Exon 1 of 10	NP_001094089.1	Q8TDN4-1
CABLES1	NM_001256438.1		c.-137+1433C>G		intron	N/A	NP_001243367.1	Q8TDN4-4
CABLES1	NR_023359.2		n.88+1452C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CABLES1	ENST00000256925.12	TSL:1 MANE Select	c.341C>G	p.Ala114Gly	missense	Exon 1 of 10	ENSP00000256925.7	Q8TDN4-1
CABLES1	ENST00000877774.1		c.341C>G	p.Ala114Gly	missense	Exon 1 of 9	ENSP00000547833.1
CABLES1	ENST00000952329.1		c.341C>G	p.Ala114Gly	missense	Exon 1 of 9	ENSP00000622388.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.66e-7

AC:

AN:

1035572

Hom.:

Cov.:

AF XY:

0.00000204

AC XY:

AN XY:

489646

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21064

American (AMR)

AF:

0.00

AC:

AN:

6780

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12000

East Asian (EAS)

AF:

0.00

AC:

AN:

22014

South Asian (SAS)

AF:

0.0000509

AC:

AN:

19662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2682

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

891808

Other (OTH)

AF:

0.00

AC:

AN:

39972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.051

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.42

M_CAP

Benign

0.074

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

3.1

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.63

REVEL

Benign

0.060

Sift

Pathogenic

0.0

Sift4G

Benign

0.34

Polyphen

0.56

Vest4

0.054

MutPred

0.33

Loss of helix (P = 0.0068)

MVP

0.38

MPC

1.1

ClinPred

0.40

GERP RS

1.6

PromoterAI

-0.0087

Neutral

(source)

Varity_R

0.24

gMVP

0.17

Mutation Taster

=85/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over