11-106053034-T-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 12/20 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
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16203177).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198439.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KBTBD3	NM_198439.3	MANE Select	c.1655A>G	p.Lys552Arg	missense	Exon 4 of 4	NP_940841.1	Q8NAB2
	KBTBD3	NM_152433.4		c.1655A>G	p.Lys552Arg	missense	Exon 3 of 3	NP_689646.2
	KBTBD3	NM_001330359.2		c.1418A>G	p.Lys473Arg	missense	Exon 3 of 3	NP_001317288.1	G3V161

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KBTBD3	ENST00000531837.2	TSL:1 MANE Select	c.1655A>G	p.Lys552Arg	missense	Exon 4 of 4	ENSP00000432163.1	Q8NAB2
	KBTBD3	ENST00000526793.5	TSL:1	c.1655A>G	p.Lys552Arg	missense	Exon 3 of 3	ENSP00000436262.1	Q8NAB2
	KBTBD3	ENST00000883713.1		c.1655A>G	p.Lys552Arg	missense	Exon 4 of 4	ENSP00000553772.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

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

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111742

Other (OTH) AF: 0.0000166 AC: 1 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.51	T
PhyloP100		3.8
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.25
Sift	Benign	0.58	T
Sift4G	Benign	0.42	T
Vest4		0.21
MVP		0.74
MPC		0.19
ClinPred		0.42	T
GERP RS		6.0
gMVP		0.70
Mutation Taster		=82/18	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

hg19: chr11-105923761;