NM_198439.3:c.1204C>G

Variant names:

• chr11-106053485-G-C
• rs938214836
• NM_198439.3:c.1204C>G

Variant summary

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

The NM_198439.3(KBTBD3):​c.1204C>G​(p.Leu402Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,576 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: KBTBD3 NM_198439.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.86
• 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=0.38979036).

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.1204C>G	p.Leu402Val	missense	Exon 4 of 4	NP_940841.1	Q8NAB2
	KBTBD3	NM_152433.4		c.1204C>G	p.Leu402Val	missense	Exon 3 of 3	NP_689646.2
	KBTBD3	NM_001330359.2		c.967C>G	p.Leu323Val	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.1204C>G	p.Leu402Val	missense	Exon 4 of 4	ENSP00000432163.1	Q8NAB2
	KBTBD3	ENST00000526793.5	TSL:1	c.1204C>G	p.Leu402Val	missense	Exon 3 of 3	ENSP00000436262.1	Q8NAB2
	KBTBD3	ENST00000883713.1		c.1204C>G	p.Leu402Val	missense	Exon 4 of 4	ENSP00000553772.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250754 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000870

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461576 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727078

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.000134 AC: 6 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111868

Other (OTH) AF: 0.0000663 AC: 4 AN: 60372

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	Benign	-0.12	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.39	T
MetaSVM	Uncertain	0.077	D
PhyloP100		3.9
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.50	N
REVEL	Uncertain	0.48
Sift	Benign	0.25	T
Sift4G	Pathogenic	0.0	D
Vest4		0.25
MVP		0.91
MPC		0.14
ClinPred		0.51	D
GERP RS		5.0
gMVP		0.47
Mutation Taster		=79/21	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

dbSNP: rs938214836; hg19: chr11-105924212;