chr18-23135878-C-T

Variant names:

• chr18-23135878-C-T
• rs1046665983
• NM_001100619.3:c.116C>T

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.116C>T​(p.Pro39Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000575 in 1,044,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. P39R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: CABLES1 NM_001100619.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473
• 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=0.09525749).

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.116C>T	p.Pro39Leu	missense	Exon 1 of 10	NP_001094089.1	Q8TDN4-1
	CABLES1	NM_001256438.1		c.-137+1208C>T		intron	N/A	NP_001243367.1	Q8TDN4-4
	CABLES1	NR_023359.2		n.88+1227C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABLES1	ENST00000256925.12	TSL:1 MANE Select	c.116C>T	p.Pro39Leu	missense	Exon 1 of 10	ENSP00000256925.7	Q8TDN4-1
	CABLES1	ENST00000877774.1		c.116C>T	p.Pro39Leu	missense	Exon 1 of 9	ENSP00000547833.1
	CABLES1	ENST00000952329.1		c.116C>T	p.Pro39Leu	missense	Exon 1 of 9	ENSP00000622388.1

Frequencies

GnomAD3 genomes AF: 0.0000341 AC: 5 AN: 146684 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000980

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000677

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

GnomAD4 exome AF: 0.00000111 AC: 1 AN: 897554 Hom.: 0 Cov.: 23 AF XY: 0.00000235 AC XY: 1 AN XY: 425006

African (AFR) AF: 0.0000590 AC: 1 AN: 16950

American (AMR) AF: 0.00 AC: 0 AN: 3484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6838

East Asian (EAS) AF: 0.00 AC: 0 AN: 6530

South Asian (SAS) AF: 0.00 AC: 0 AN: 19314

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1940

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 805996

Other (OTH) AF: 0.00 AC: 0 AN: 30748

GnomAD4 genome AF: 0.0000341 AC: 5 AN: 146684 Hom.: 0 Cov.: 32 AF XY: 0.0000280 AC XY: 2 AN XY: 71342

African (AFR) AF: 0.0000980 AC: 4 AN: 40812

American (AMR) AF: 0.0000677 AC: 1 AN: 14762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3390

East Asian (EAS) AF: 0.00 AC: 0 AN: 5106

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65942

Other (OTH) AF: 0.00 AC: 0 AN: 2030

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000718

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.37	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.47
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.058
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.19	T
Polyphen		0.017	B
Vest4		0.20
MutPred		0.13		Gain of helix (P = 0.005)
MVP		0.49
MPC		1.1
ClinPred		0.49	T
GERP RS		1.8
PromoterAI		-0.057	Neutral
Varity_R		0.061
gMVP		0.20
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: rs1046665983; hg19: chr18-20715842;