Variant 11-106053250-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000531837.2(KBTBD3):c.1439A>G(p.Asn480Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,613,708 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 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

KBTBD3
ENST00000531837.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

Variant links:

Genes affected

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

KBTBD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027184844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KBTBD3	NM_198439.3 linkuse as main transcript	c.1439A>G	p.Asn480Ser	missense_variant	4/4	ENST00000531837.2	NP_940841.1	Q8NAB2A0A024R3B5A8K1K0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KBTBD3	ENST00000531837.2 linkuse as main transcript	c.1439A>G	p.Asn480Ser	missense_variant	4/4	1	NM_198439.3	ENSP00000432163.1	Q8NAB2
KBTBD3	ENST00000526793.5 linkuse as main transcript	c.1439A>G	p.Asn480Ser	missense_variant	3/3	1		ENSP00000436262.1	Q8NAB2
KBTBD3	ENST00000534815.1 linkuse as main transcript	c.1202A>G	p.Asn401Ser	missense_variant	2/2	5		ENSP00000431910.1	G3V161

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000239

AC:

AN:

250664

Hom.:

AF XY:

0.000229

AC XY:

AN XY:

135548

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00407

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.0000883

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.0000992

AC:

145

AN:

1461456

Hom.:

Cov.:

AF XY:

0.000103

AC XY:

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00344

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

AF:

0.000177

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000300

Hom.:

Bravo

AF:

0.000136

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

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

May 04, 2022

The c.1439A>G (p.N480S) 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 1439, causing the asparagine (N) at amino acid position 480 to be replaced by a serine (S). 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

0.082

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;.;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.027

T;T;T

MetaSVM

Benign

-0.61

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.3

N;D;D

REVEL

Uncertain

0.32

Sift

Benign

0.10

T;T;T

Sift4G

Uncertain

0.047

D;D;D

Vest4

0.48

MVP

0.86

MPC

0.12

ClinPred

0.15

GERP RS

6.0

gMVP

0.31

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