rs748092018

chr13-41193050-T-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6

The NM_032138.7(KBTBD7):c.1208A>C(p.Lys403Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,614,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

KBTBD7
NM_032138.7 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.77

Variant links:

Genes affected

KBTBD7 (HGNC:25266): (kelch repeat and BTB domain containing 7) The protein encoded by this gene is a transcriptional activator, having been shown to increase the transcription of activator protein-1 and serum response element. The encoded protein can also form a complex with KBTBD6 and CUL3, which regulates the ubiquitylation and degradation of TIAM1, which is a regulator of RAC1. [provided by RefSeq, Jul 2016]

KBTBD7 links:

KBTBD6-DT (HGNC:56824): (KBTBD6 divergent transcript)

KBTBD6-DT links:

LOC101929140 (HGNC:):

LOC101929140 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16197419).

BP6

Variant 13-41193050-T-G is Benign according to our data. Variant chr13-41193050-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 254109.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KBTBD7	NM_032138.7 linkuse as main transcript	c.1208A>C	p.Lys403Thr	missense_variant	1/1	ENST00000379483.4
LOC101929140	NR_120423.1 linkuse as main transcript	n.350+30647T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
KBTBD7	ENST00000379483.4 linkuse as main transcript	c.1208A>C	p.Lys403Thr	missense_variant	1/1		NM_032138.7	P1
KBTBD6-DT	ENST00000619407.4 linkuse as main transcript	n.339+30647T>G		intron_variant, non_coding_transcript_variant		2
KBTBD6-DT	ENST00000661006.1 linkuse as main transcript	n.245+30647T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251494

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Oromandibular-limb hypogenesis spectrum

Benign:1

Likely benign, no assertion criteria provided

research

CHU Sainte-Justine Research Center, University of Montreal

Aug 12, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.16

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.24

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.056

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.63

M_CAP

Benign

0.019

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.28

Sift

Benign

0.21

Sift4G

Benign

0.21

Polyphen

0.0060

Vest4

0.24

MutPred

0.47

Loss of ubiquitination at K403 (P = 0.0155);

MVP

0.74

MPC

0.85

ClinPred

0.062

GERP RS

4.9

Varity_R

0.22

gMVP

0.84

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