13-49376996-T-A

Variant names:

• chr13-49376996-T-A
• NM_001079670.3:c.247A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001079670.3(CAB39L):​c.247A>T​(p.Ile83Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAB39L NM_001079670.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.65
• Publications: 0 publications found

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]

ENSG00000297916 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.346914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAB39L	NM_001079670.3	c.247A>T	p.Ile83Leu	missense_variant	Exon 5 of 11	ENST00000409308.6	NP_001073138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAB39L	ENST00000409308.6	c.247A>T	p.Ile83Leu	missense_variant	Exon 5 of 11	1	NM_001079670.3	ENSP00000386375.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.247A>T (p.I83L) alteration is located in exon 3 (coding exon 2) of the CAB39L gene. This alteration results from a A to T substitution at nucleotide position 247, causing the isoleucine (I) at amino acid position 83 to be replaced by a leucine (L). 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	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.079	T;T;T;T;T;T;T;T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.021
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	.;.;D;.;D;.;D;D;D
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.35	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.94	L;L;L;L;.;L;.;.;.
PhyloP100		2.7
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.4	N;.;N;N;N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.17	T;.;T;T;T;T;T;T;T
Sift4G	Benign	0.17	T;T;T;T;T;T;.;.;.
Polyphen		0.023	B;B;B;B;.;B;.;.;.
Vest4		0.41
MutPred		0.69		Loss of catalytic residue at L88 (P = 0.0319);Loss of catalytic residue at L88 (P = 0.0319);Loss of catalytic residue at L88 (P = 0.0319);Loss of catalytic residue at L88 (P = 0.0319);.;Loss of catalytic residue at L88 (P = 0.0319);Loss of catalytic residue at L88 (P = 0.0319);Loss of catalytic residue at L88 (P = 0.0319);Loss of catalytic residue at L88 (P = 0.0319);
MVP		0.36
MPC		0.16
ClinPred		0.61	D
GERP RS		5.5
PromoterAI		-0.0040	Neutral
Varity_R		0.53
gMVP		0.40
Mutation Taster		=77/23	polymorphism

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

hg19: chr13-49951132;