Variant 2-230818587-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.909A>G(p.Ile303Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CAB39
NM_016289.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.225

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:

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/exons	MANE
CAB39	NM_016289.4 linkuse as main transcript	c.909A>G	p.Ile303Met	missense_variant	9/9	ENST00000258418.10
CAB39	NM_001130849.2 linkuse as main transcript	c.909A>G	p.Ile303Met	missense_variant	9/9
CAB39	NM_001130850.2 linkuse as main transcript	c.909A>G	p.Ile303Met	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CAB39	ENST00000258418.10 linkuse as main transcript	c.909A>G	p.Ile303Met	missense_variant	9/9	1	NM_016289.4	P1
CAB39	ENST00000410084.7 linkuse as main transcript	c.909A>G	p.Ile303Met	missense_variant	9/9	1		P1
CAB39	ENST00000409788.7 linkuse as main transcript	c.909A>G	p.Ile303Met	missense_variant	9/9	2		P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000478

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251420

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461784

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727202

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000113

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

Dec 28, 2023

The c.909A>G (p.I303M) alteration is located in exon 9 (coding exon 8) of the CAB39 gene. This alteration results from a A to G substitution at nucleotide position 909, causing the isoleucine (I) at amino acid position 303 to be replaced by a methionine (M). 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

0.21

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.18

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.37

T;T;T;T

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.80

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.70

D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.8

N;N;N;.

REVEL

Uncertain

0.33

Sift

Uncertain

0.0050

D;D;D;.

Sift4G

Uncertain

0.046

D;D;D;D

Polyphen

0.88

P;P;P;.

Vest4

0.64

MutPred

0.61

Gain of disorder (P = 0.0651);Gain of disorder (P = 0.0651);Gain of disorder (P = 0.0651);.;

MVP

0.61

MPC

0.97

ClinPred

0.62

GERP RS

0.41

Varity_R

0.74

gMVP

0.38

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