Genetic Variant CAB39L:p.Val80Leu (chr13-49377005-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001079670.3(CAB39L):c.238G>C(p.Val80Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CAB39L
NM_001079670.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.36

Publications

0 publications found

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:

ENSG00000297916 (HGNC:):

ENSG00000297916 links:

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ACMG classification

Classification was made for transcript

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=0.14559534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAB39L	NM_001079670.3 link	c.238G>C	p.Val80Leu	missense_variant	Exon 5 of 11	ENST00000409308.6	NP_001073138.1	Q9H9S4A0A024RDT3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAB39L	ENST00000409308.6 link	c.238G>C	p.Val80Leu	missense_variant	Exon 5 of 11	1	NM_001079670.3	ENSP00000386375.1		Q9H9S4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460792

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726742

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86092

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111254

Other (OTH)

AF:

0.00

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.038

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

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.099

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.84

.;.;T;.;T;.;T;D;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.15

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

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.74

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

PhyloP100

2.4

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.16

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

REVEL

Benign

0.12

Sift

Benign

0.66

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

Sift4G

Benign

0.69

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

Polyphen

0.0

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

Vest4

0.20

MutPred

0.35

Loss of catalytic residue at V80 (P = 0.0648);Loss of catalytic residue at V80 (P = 0.0648);Loss of catalytic residue at V80 (P = 0.0648);Loss of catalytic residue at V80 (P = 0.0648);.;Loss of catalytic residue at V80 (P = 0.0648);Loss of catalytic residue at V80 (P = 0.0648);Loss of catalytic residue at V80 (P = 0.0648);Loss of catalytic residue at V80 (P = 0.0648);

MVP

0.29

MPC

0.15

ClinPred

0.62

GERP RS

5.5

PromoterAI

0.0085

Neutral

(source)

Varity_R

0.22

gMVP

0.20

Mutation Taster

=62/38

polymorphism

(source)

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

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chr13-49377005-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over