11-106054153-T-A

Position:

• chr11-106054153-T-A

Variant summary

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

The NM_198439.3(KBTBD3):​c.536A>T​(p.His179Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 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: KBTBD3 NM_198439.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89

Genes affected

KBTBD3 (HGNC:22934): (kelch repeat and BTB domain containing 3)

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=0.24490505).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KBTBD3	NM_198439.3	c.536A>T	p.His179Leu	missense_variant	4/4	ENST00000531837.2	NP_940841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KBTBD3	ENST00000531837.2	c.536A>T	p.His179Leu	missense_variant	4/4	1	NM_198439.3	ENSP00000432163	P1
KBTBD3	ENST00000526793.5	c.536A>T	p.His179Leu	missense_variant	3/3	1		ENSP00000436262	P1
KBTBD3	ENST00000534815.1	c.299A>T	p.His100Leu	missense_variant	2/2	5		ENSP00000431910

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Mar 24, 2023

The c.536A>T (p.H179L) alteration is located in exon 4 (coding exon 2) of the KBTBD3 gene. This alteration results from a A to T substitution at nucleotide position 536, causing the histidine (H) at amino acid position 179 to be replaced by a leucine (L). 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	Benign	0.088
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Benign	0.96
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.052
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.61	T;.;T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.70	T
MutationTaster	Benign	0.75	D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.025	D;T;T
Sift4G	Uncertain	0.058	T;T;T
Vest4		0.38
MVP		0.77
MPC		0.17
ClinPred		0.38	T
GERP RS		3.3
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr11-105924880; COSMIC: COSV73241185; COSMIC: COSV73241185;