rs757820177

Variant names:

• chr13-49350856-C-A
• rs757820177
• NM_001079670.3:c.452G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-49350856-C-A
• chr13-49350856-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001079670.3(CAB39L):​c.452G>T​(p.Arg151Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. R151Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAB39L NM_001079670.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.88
• Publications: 6 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.968

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAB39L	NM_001079670.3	c.452G>T	p.Arg151Leu	missense_variant	Exon 7 of 11	ENST00000409308.6	NP_001073138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAB39L	ENST00000409308.6	c.452G>T	p.Arg151Leu	missense_variant	Exon 7 of 11	1	NM_001079670.3	ENSP00000386375.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;T;T;T;T;T;T;T
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	.;.;D;.;D;D;.;D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.97	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.38	T
MutationAssessor	Pathogenic	3.5	M;M;M;M;.;.;M;.
PhyloP100		7.9
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-6.3	D;.;D;D;D;D;D;D
REVEL	Pathogenic	0.76
Sift	Uncertain	0.0010	D;.;D;D;D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;D;D;D;.
Polyphen		1.0	D;D;D;D;.;.;D;.
Vest4		0.94
MutPred		0.90		Gain of catalytic residue at R151 (P = 0.1125);Gain of catalytic residue at R151 (P = 0.1125);Gain of catalytic residue at R151 (P = 0.1125);Gain of catalytic residue at R151 (P = 0.1125);.;.;Gain of catalytic residue at R151 (P = 0.1125);Gain of catalytic residue at R151 (P = 0.1125);
MVP		0.61
MPC		0.73
ClinPred		1.0	D
GERP RS		5.6
PromoterAI		-0.038	Neutral
Varity_R		0.86
gMVP		0.71
Mutation Taster		=18/82	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs757820177; hg19: chr13-49924992;