Variant chr13-49310901-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001079670.3(CAB39L):c.927A>C(p.Gln309His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00037 in 1,614,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

CAB39L
NM_001079670.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.769

Variant links:

Genes affected

CAB39L (HGNC:20290): (calcium binding protein 39 like) Predicted to enable protein serine/threonine kinase activator activity. Predicted to be involved in intracellular signal transduction. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

CAB39L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052845776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAB39L	NM_001079670.3 linkuse as main transcript	c.927A>C	p.Gln309His	missense_variant	11/11	ENST00000409308.6	NP_001073138.1	Q9H9S4A0A024RDT3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAB39L	ENST00000409308.6 linkuse as main transcript	c.927A>C	p.Gln309His	missense_variant	11/11	1	NM_001079670.3	ENSP00000386375.1		Q9H9S4

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.000676

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000151

AC:

AN:

251400

Hom.:

AF XY:

0.000132

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000282

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000374

AC:

547

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000406

AC XY:

295

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000467

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.000328

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000722

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:

0.000676

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000545

Hom.:

Bravo

AF:

0.000336

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000189

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000296

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

May 15, 2024

The c.927A>C (p.Q309H) alteration is located in exon 9 (coding exon 8) of the CAB39L gene. This alteration results from a A to C substitution at nucleotide position 927, causing the glutamine (Q) at amino acid position 309 to be replaced by a histidine (H). 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

Uncertain

0.54

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.36

CADD

Benign

4.1

DANN

Benign

0.22

DEOGEN2

Benign

0.025

T;T;T;T;T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.92

.;.;D;.;D;D;.

M_CAP

Benign

0.020

MetaRNN

Benign

0.053

T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.91

N;N;N;N;.;.;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

4.6

N;.;N;N;N;N;N

REVEL

Uncertain

0.33

Sift

Benign

1.0

T;.;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T;T

Polyphen

0.015

B;B;B;B;.;.;B

Vest4

0.59

MutPred

0.36

Gain of catalytic residue at E311 (P = 0.1153);Gain of catalytic residue at E311 (P = 0.1153);Gain of catalytic residue at E311 (P = 0.1153);Gain of catalytic residue at E311 (P = 0.1153);.;.;Gain of catalytic residue at E311 (P = 0.1153);

MVP

0.17

MPC

0.15

ClinPred

0.0064

GERP RS

-4.6

Varity_R

0.31

gMVP

0.49

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