11-106053034-T-C

Variant names:

• chr11-106053034-T-C
• NM_198439.3:c.1655A>G

Variant summary

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

The NM_198439.3(KBTBD3):​c.1655A>G​(p.Lys552Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000171 in 1,461,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: KBTBD3 NM_198439.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.75

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=0.16203177).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KBTBD3	NM_198439.3	c.1655A>G	p.Lys552Arg	missense_variant	Exon 4 of 4	ENST00000531837.2	NP_940841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KBTBD3	ENST00000531837.2	c.1655A>G	p.Lys552Arg	missense_variant	Exon 4 of 4	1	NM_198439.3	ENSP00000432163.1
KBTBD3	ENST00000526793.5	c.1655A>G	p.Lys552Arg	missense_variant	Exon 3 of 3	1		ENSP00000436262.1
KBTBD3	ENST00000534815.1	c.1418A>G	p.Lys473Arg	missense_variant	Exon 2 of 2	5		ENSP00000431910.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1461426 Hom.: 0 Cov.: 33 AF XY: 0.0000165 AC XY: 12 AN XY: 727024

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000216

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 29, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1655A>G (p.K552R) alteration is located in exon 4 (coding exon 2) of the KBTBD3 gene. This alteration results from a A to G substitution at nucleotide position 1655, causing the lysine (K) at amino acid position 552 to be replaced by an arginine (R). 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	0.091
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	18
DANN	Uncertain	0.98
Eigen	Benign	-0.0065
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.84	T;.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.51	T
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.87	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.58	T;T;T
Sift4G	Benign	0.42	T;T;T
Vest4		0.21
MVP		0.74
MPC		0.19
ClinPred		0.42	T
GERP RS		6.0
gMVP		0.70

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: chr11-105923761;