13-49332009-T-C

Variant names:

• chr13-49332009-T-C
• rs746603549
• NM_001079670.3:c.772A>G

Variant summary

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

The NM_001079670.3(CAB39L):​c.772A>G​(p.Met258Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. M258L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CAB39L NM_001079670.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.28
• 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.772A>G	p.Met258Val	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.772A>G	p.Met258Val	missense_variant	Exon 10 of 11	1	NM_001079670.3	ENSP00000386375.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251438 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461724 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 727180

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111876

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T;T;T;T;T;T;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	.;.;D;.;D;D;.
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.49	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M;M;M;.;.;M
PhyloP100		6.3
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.1	D;.;D;D;D;D;D
REVEL	Benign	0.10
Sift	Benign	0.054	T;.;T;T;T;T;T
Sift4G	Benign	0.096	T;T;T;T;T;T;T
Polyphen		0.71	P;P;P;P;.;.;P
Vest4		0.41
MutPred		0.51		Loss of disorder (P = 0.1263);Loss of disorder (P = 0.1263);Loss of disorder (P = 0.1263);Loss of disorder (P = 0.1263);.;.;Loss of disorder (P = 0.1263);
MVP		0.45
MPC		0.31
ClinPred		0.65	D
GERP RS		4.6
Varity_R		0.65
gMVP		0.42
Mutation Taster		=57/43	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

dbSNP: rs746603549; hg19: chr13-49906145;