18-23253755-C-T

Variant summary

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

The NM_001100619.3(CABLES1):​c.1580C>T​(p.Ala527Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CABLES1
NM_001100619.3 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17
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]
TMEM241 (HGNC:31723): (transmembrane protein 241) Predicted to enable antiporter activity. Predicted to be involved in carbohydrate transport and transmembrane transport. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CABLES1NM_001100619.3 linkc.1580C>T p.Ala527Val missense_variant Exon 9 of 10 ENST00000256925.12 NP_001094089.1 Q8TDN4-1A7K6Y5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CABLES1ENST00000256925.12 linkc.1580C>T p.Ala527Val missense_variant Exon 9 of 10 1 NM_001100619.3 ENSP00000256925.7 Q8TDN4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461832
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
4
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1580C>T (p.A527V) alteration is located in exon 9 (coding exon 9) of the CABLES1 gene. This alteration results from a C to T substitution at nucleotide position 1580, causing the alanine (A) at amino acid position 527 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
Pathogenic
0.72
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.0
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
.;T;.
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Benign
0.014
T
MetaRNN
Uncertain
0.65
D;D;D
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.9
.;L;.
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-1.6
N;N;N
REVEL
Benign
0.23
Sift
Benign
0.049
D;D;D
Sift4G
Uncertain
0.033
D;D;D
Polyphen
1.0, 0.88
.;D;P
Vest4
0.79
MutPred
0.26
.;Loss of ubiquitination at K525 (P = 0.0801);.;
MVP
0.54
MPC
1.1
ClinPred
0.90
D
GERP RS
4.9
Varity_R
0.29
gMVP
0.78

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs529533048; hg19: chr18-20833719; COSMIC: COSV56932308; COSMIC: COSV56932308; API