rs1598791278

Variant names:

• chr18-23135926-C-G
• rs1598791278
• NM_001100619.3:c.164C>G

Your query was ambiguous. Multiple possible variants found:

• chr18-23135926-C-G
• chr18-23135926-C-A

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.164C>G​(p.Pro55Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000677 in 147,654 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CABLES1 NM_001100619.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0610
• 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=0.116754055).

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.164C>G	p.Pro55Arg	missense	Exon 1 of 10	NP_001094089.1	Q8TDN4-1
	CABLES1	NM_001256438.1		c.-137+1256C>G		intron	N/A	NP_001243367.1	Q8TDN4-4
	CABLES1	NR_023359.2		n.88+1275C>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.164C>G	p.Pro55Arg	missense	Exon 1 of 10	ENSP00000256925.7	Q8TDN4-1
	CABLES1	ENST00000877774.1		c.164C>G	p.Pro55Arg	missense	Exon 1 of 9	ENSP00000547833.1
	CABLES1	ENST00000952329.1		c.164C>G	p.Pro55Arg	missense	Exon 1 of 9	ENSP00000622388.1

Frequencies

GnomAD3 genomes AF: 0.00000677 AC: 1 AN: 147654 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 957418 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 456088

African (AFR) AF: 0.00 AC: 0 AN: 18992

American (AMR) AF: 0.00 AC: 0 AN: 5566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8472

East Asian (EAS) AF: 0.00 AC: 0 AN: 11896

South Asian (SAS) AF: 0.00 AC: 0 AN: 19802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2272

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 845050

Other (OTH) AF: 0.00 AC: 0 AN: 34134

GnomAD4 genome AF: 0.00000677 AC: 1 AN: 147654 Hom.: 0 Cov.: 32 AF XY: 0.0000139 AC XY: 1 AN XY: 71856

African (AFR) AF: 0.00 AC: 0 AN: 40980

American (AMR) AF: 0.00 AC: 0 AN: 14854

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3404

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5122

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66256

Other (OTH) AF: 0.00 AC: 0 AN: 2044

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	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.39	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.061
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	0.60	N
REVEL	Benign	0.067
Sift	Uncertain	0.010	D
Sift4G	Benign	0.51	T
Polyphen		0.56	P
Vest4		0.17
MutPred		0.10		Gain of helix (P = 0.0164)
MVP		0.55
MPC		1.2
ClinPred		0.44	T
GERP RS		0.90
PromoterAI		0.062	Neutral
Varity_R		0.070
gMVP		0.12

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: rs1598791278; hg19: chr18-20715890;