13-49376983-T-G

Variant names:

• chr13-49376983-T-G
• rs764292251
• NM_001079670.3:c.260A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001079670.3(CAB39L):​c.260A>C​(p.Gln87Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000686 in 1,458,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. Q87R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: CAB39L NM_001079670.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.93
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24518809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAB39L	NM_001079670.3	c.260A>C	p.Gln87Pro	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.260A>C	p.Gln87Pro	missense_variant	Exon 5 of 11	1	NM_001079670.3	ENSP00000386375.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000401 AC: 10 AN: 249618 AF XY: 0.0000296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000293

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: 0.00000686 AC: 10 AN: 1458120 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4 AN XY: 725470

African (AFR) AF: 0.00 AC: 0 AN: 33280

American (AMR) AF: 0.000225 AC: 10 AN: 44396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25964

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 85588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109918

Other (OTH) AF: 0.00 AC: 0 AN: 60230

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	20
DANN	Benign	0.32
DEOGEN2	Benign	0.072	T;T;T;T;T;T;T;T;T
Eigen	Benign	-0.048
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	.;.;D;.;D;.;D;D;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.25	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.20	N;N;N;N;.;N;.;.;.
PhyloP100		7.9
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.65	N;.;N;N;N;N;N;N;N
REVEL	Benign	0.22
Sift	Benign	1.0	T;.;T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;.;.;.
Polyphen		0.0	B;B;B;B;.;B;.;.;.
Vest4		0.84
MutPred		0.47		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);.;Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.33
MPC		0.19
ClinPred		0.20	T
GERP RS		5.6
PromoterAI		0.014	Neutral
Varity_R		0.62
gMVP		0.54
Mutation Taster		=45/55	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: rs764292251; hg19: chr13-49951119;