Variant 8-2001811-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000320248.4(KBTBD11):c.619G>T(p.Val207Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,230,222 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: 𝑓 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

KBTBD11
ENST00000320248.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.77

Variant links:

Genes affected

KBTBD11 (HGNC:29104): (kelch repeat and BTB domain containing 11)

KBTBD11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.23460144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KBTBD11	NM_014867.3 linkuse as main transcript	c.619G>T	p.Val207Leu	missense_variant	2/2	ENST00000320248.4	NP_055682.1
KBTBD11	XM_011534772.3 linkuse as main transcript	c.619G>T	p.Val207Leu	missense_variant	3/3		XP_011533074.1
KBTBD11	XM_017014116.2 linkuse as main transcript	c.619G>T	p.Val207Leu	missense_variant	3/3		XP_016869605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KBTBD11	ENST00000320248.4 linkuse as main transcript	c.619G>T	p.Val207Leu	missense_variant	2/2	1	NM_014867.3	ENSP00000321544	P1

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

149224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000597

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000352

AC:

AN:

1080998

Hom.:

Cov.:

AF XY:

0.0000309

AC XY:

AN XY:

517574

show subpopulations

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:

0.0000401

Gnomad4 OTH exome

AF:

0.0000236

GnomAD4 genome

AF:

0.0000268

AC:

AN:

149224

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72744

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000597

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 19, 2021

The c.619G>T (p.V207L) alteration is located in exon 2 (coding exon 1) of the KBTBD11 gene. This alteration results from a G to T substitution at nucleotide position 619, causing the valine (V) at amino acid position 207 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

Pathogenic

0.69

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.93

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.97

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.97

PROVEAN

Benign

-0.91

REVEL

Uncertain

0.29

Sift

Benign

0.41

Sift4G

Benign

0.23

Polyphen

0.21

Vest4

0.26

MutPred

0.47

Loss of catalytic residue at V207 (P = 0.0444);

MVP

0.58

MPC

2.2

ClinPred

0.85

GERP RS

3.9

Varity_R

0.32

gMVP

0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over