Variant 2-230790905-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016289.4(CAB39):c.148A>G(p.Met50Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,456,022 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: 0.000016 ( 0 hom. )

Consequence

CAB39
NM_016289.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.36

Variant links:

Genes affected

CAB39 (HGNC:20292): (calcium binding protein 39) Enables kinase binding activity and protein serine/threonine kinase activator activity. Involved in intracellular signal transduction; peptidyl-serine phosphorylation; and positive regulation of protein phosphorylation. Located in extracellular exosome. Implicated in hepatocellular carcinoma. Biomarker of hepatocellular carcinoma and pancreatic cancer. [provided by Alliance of Genome Resources, Apr 2022]

CAB39 links:

CAB39 (HGNC:):

CAB39 links:

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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/exons	MANE	Protein	UniProt
CAB39	NM_016289.4 linkuse as main transcript	c.148A>G	p.Met50Val	missense_variant	3/9	ENST00000258418.10	NP_057373.1	Q9Y376A0A024R496

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAB39	ENST00000258418.10 linkuse as main transcript	c.148A>G	p.Met50Val	missense_variant	3/9	1	NM_016289.4	ENSP00000258418.5		Q9Y376

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000815

AC:

AN:

245542

Hom.:

AF XY:

0.00000754

AC XY:

AN XY:

132598

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1456022

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

724112

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 21, 2024

The c.148A>G (p.M50V) alteration is located in exon 3 (coding exon 2) of the CAB39 gene. This alteration results from a A to G substitution at nucleotide position 148, causing the methionine (M) at amino acid position 50 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

Benign

0.12

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.040

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.31

T;T;T;T

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

.;.;D;D

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.56

D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;L;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.3

N;N;N;.

REVEL

Benign

0.24

Sift

Benign

0.12

T;T;T;.

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.010

B;B;B;.

Vest4

0.71

MutPred

0.61

Gain of methylation at K51 (P = 0.0236);Gain of methylation at K51 (P = 0.0236);Gain of methylation at K51 (P = 0.0236);Gain of methylation at K51 (P = 0.0236);

MVP

0.61

MPC

0.68

ClinPred

0.55

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.44

gMVP

0.69

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over