11-106053317-C-T

Variant names:

• chr11-106053317-C-T
• NM_198439.3:c.1372G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198439.3(KBTBD3):​c.1372G>A​(p.Val458Ile) 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. 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: 4.57
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33205622).

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.1372G>A	p.Val458Ile	missense	Exon 4 of 4	NP_940841.1	Q8NAB2
	KBTBD3	NM_152433.4		c.1372G>A	p.Val458Ile	missense	Exon 3 of 3	NP_689646.2
	KBTBD3	NM_001330359.2		c.1135G>A	p.Val379Ile	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.1372G>A	p.Val458Ile	missense	Exon 4 of 4	ENSP00000432163.1	Q8NAB2
	KBTBD3	ENST00000526793.5	TSL:1	c.1372G>A	p.Val458Ile	missense	Exon 3 of 3	ENSP00000436262.1	Q8NAB2
	KBTBD3	ENST00000883713.1		c.1372G>A	p.Val458Ile	missense	Exon 4 of 4	ENSP00000553772.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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	0.11
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.47	T
PhyloP100		4.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.24
Sift	Benign	0.061	T
Sift4G	Benign	0.17	T
Vest4		0.28
MVP		0.68
MPC		0.21
ClinPred		0.86	D
GERP RS		6.0
gMVP		0.38
Mutation Taster		=90/10	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: chr11-105924044; COSMIC: COSV101595704; COSMIC: COSV101595704;