rs2919360

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001101362.3(KBTBD13):c.1200T>C(p.Gly400Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,606,120 control chromosomes in the GnomAD database, including 798,499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 74770 hom., cov: 36)

Exomes 𝑓: 1.0 ( 723729 hom. )

Consequence

KBTBD13
NM_001101362.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -4.21

Variant links:

Genes affected

KBTBD13 (HGNC:37227): (kelch repeat and BTB domain containing 13) The gene belongs to a family of genes encoding proteins containing a BTB domain and several kelch repeats. The BTB domain functions as a protein-protein interaction module, which includes an ability to self-associate or to interact with non-BTB domain-containing proteins. The kelch motif typically occurs in groups of five to seven repeats, and has been found in proteins with diverse functions. Known functions of these family members include transcription regulation, ion channel tetramerization and gating, protein ubiquitination or degradation, and cytoskeleton regulation. The exact function of this family member has yet to be determined. [provided by RefSeq, Jun 2010]

KBTBD13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 15-65078015-T-C is Benign according to our data. Variant chr15-65078015-T-C is described in ClinVar as [Benign]. Clinvar id is 129307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-65078015-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.21 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KBTBD13	NM_001101362.3 linkuse as main transcript	c.1200T>C	p.Gly400Gly	synonymous_variant	1/1	ENST00000432196.5	NP_001094832.1	C9JR72

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KBTBD13	ENST00000432196.5 linkuse as main transcript	c.1200T>C	p.Gly400Gly	synonymous_variant	1/1	6	NM_001101362.3	ENSP00000388723.2		C9JR72

Frequencies

GnomAD3 genomes

AF:

0.991

AC:

150837

AN:

152258

Hom.:

74715

Cov.:

show subpopulations

Gnomad AFR

AF:

0.973

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.993

Gnomad ASJ

AF:

0.976

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.991

GnomAD3 exomes

AF:

0.996

AC:

234485

AN:

235450

Hom.:

116768

AF XY:

0.996

AC XY:

129484

AN XY:

129960

show subpopulations

Gnomad AFR exome

AF:

0.972

Gnomad AMR exome

AF:

0.996

Gnomad ASJ exome

AF:

0.978

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.998

Gnomad OTH exome

AF:

0.996

GnomAD4 exome

AF:

0.998

AC:

1450572

AN:

1453744

Hom.:

723729

Cov.:

AF XY:

0.998

AC XY:

722027

AN XY:

723550

show subpopulations

Gnomad4 AFR exome

AF:

0.972

Gnomad4 AMR exome

AF:

0.995

Gnomad4 ASJ exome

AF:

0.980

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.995

GnomAD4 genome

AF:

0.991

AC:

150951

AN:

152376

Hom.:

74770

Cov.:

AF XY:

0.991

AC XY:

73813

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.973

Gnomad4 AMR

AF:

0.993

Gnomad4 ASJ

AF:

0.976

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.991

Alfa

AF:

0.994

Hom.:

30450

Bravo

AF:

0.989

Asia WGS

AF:

0.998

AC:

3471

AN:

3478

EpiCase

AF:

0.997

EpiControl

AF:

0.997

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 22, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Nemaline myopathy 6

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.3

DANN

Benign

0.62

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