13-41130942-C-T

Position:

• chr13-41130942-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152903.5(KBTBD6):​c.1570G>A​(p.Glu524Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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: KBTBD6 NM_152903.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.83

Genes affected

KBTBD6 (HGNC:25340): (kelch repeat and BTB domain containing 6) Involved in proteasome-mediated ubiquitin-dependent protein catabolic process; protein K48-linked ubiquitination; and regulation of Rac protein signal transduction. Located in cytoplasm and nucleus. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KBTBD6	NM_152903.5	c.1570G>A	p.Glu524Lys	missense_variant	1/1	ENST00000379485.2	NP_690867.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KBTBD6	ENST00000379485.2	c.1570G>A	p.Glu524Lys	missense_variant	1/1	6	NM_152903.5	ENSP00000368799.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 02, 2024

The c.1570G>A (p.E524K) alteration is located in exon 1 (coding exon 1) of the KBTBD6 gene. This alteration results from a G to A substitution at nucleotide position 1570, causing the glutamic acid (E) at amino acid position 524 to be replaced by a lysine (K). 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	Uncertain	0.49
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.048
Eigen_PC	Benign	-0.045
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.20
Sift	Benign	0.50	T
Sift4G	Uncertain	0.031	D
Polyphen		0.53	P
Vest4		0.22
MutPred		0.64		Gain of ubiquitination at E524 (P = 0.0337);
MVP		0.38
MPC		2.1
ClinPred		0.77	D
GERP RS		2.9
Varity_R		0.17
gMVP		0.87

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-41705078;