13-49332042-T-G

Variant names:

• chr13-49332042-T-G
• rs186705879
• NM_001079670.3:c.739A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001079670.3(CAB39L):​c.739A>C​(p.Lys247Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K247E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CAB39L NM_001079670.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAB39L	NM_001079670.3	c.739A>C	p.Lys247Gln	missense_variant	Exon 10 of 11	ENST00000409308.6	NP_001073138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAB39L	ENST00000409308.6	c.739A>C	p.Lys247Gln	missense_variant	Exon 10 of 11	1	NM_001079670.3	ENSP00000386375.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	T;T;T;T;T;T;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	.;.;D;.;D;D;.
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.45	T;T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.6	L;L;L;L;.;.;L
PhyloP100		2.9
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.2	N;.;N;N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.097	T;.;T;T;T;T;T
Sift4G	Benign	0.16	T;T;T;T;T;T;T
Polyphen		0.96	D;D;D;D;.;.;D
Vest4		0.60
MutPred		0.59		Loss of methylation at K247 (P = 0.0186);Loss of methylation at K247 (P = 0.0186);Loss of methylation at K247 (P = 0.0186);Loss of methylation at K247 (P = 0.0186);.;.;Loss of methylation at K247 (P = 0.0186);
MVP		0.53
MPC		0.20
ClinPred		0.72	D
GERP RS		5.9
Varity_R		0.30
gMVP		0.17
Mutation Taster		=48/52	disease causing

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

dbSNP: rs186705879; hg19: chr13-49906178;