15-65077057-C-T

Position:

chr15-65077057-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001101362.3(KBTBD13):c.242C>T(p.Ala81Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,516,914 control chromosomes in the GnomAD database, including 127,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 17251 hom., cov: 34)

Exomes 𝑓: 0.40 ( 110636 hom. )

Consequence

KBTBD13
NM_001101362.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 7.55

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.249197E-6).

BP6

Variant 15-65077057-C-T is Benign according to our data. Variant chr15-65077057-C-T is described in ClinVar as [Benign]. Clinvar id is 129308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-65077057-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.692 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.242C>T	p.Ala81Val	missense_variant	1/1	ENST00000432196.5	NP_001094832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KBTBD13	ENST00000432196.5 linkuse as main transcript	c.242C>T	p.Ala81Val	missense_variant	1/1		NM_001101362.3	ENSP00000388723	P1

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70369

AN:

151868

Hom.:

17224

Cov.:

show subpopulations

Gnomad AFR

AF:

0.600

Gnomad AMI

AF:

0.387

Gnomad AMR

AF:

0.480

Gnomad ASJ

AF:

0.324

Gnomad EAS

AF:

0.711

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.403

Gnomad MID

AF:

0.433

Gnomad NFE

AF:

0.385

Gnomad OTH

AF:

0.440

GnomAD3 exomes

AF:

0.451

AC:

52069

AN:

115552

Hom.:

12642

AF XY:

0.435

AC XY:

27899

AN XY:

64092

show subpopulations

Gnomad AFR exome

AF:

0.661

Gnomad AMR exome

AF:

0.538

Gnomad ASJ exome

AF:

0.342

Gnomad EAS exome

AF:

0.745

Gnomad SAS exome

AF:

0.343

Gnomad FIN exome

AF:

0.397

Gnomad NFE exome

AF:

0.400

Gnomad OTH exome

AF:

0.431

GnomAD4 exome

AF:

0.396

AC:

540189

AN:

1364938

Hom.:

110636

Cov.:

AF XY:

0.393

AC XY:

264751

AN XY:

673102

show subpopulations

Gnomad4 AFR exome

AF:

0.612

Gnomad4 AMR exome

AF:

0.527

Gnomad4 ASJ exome

AF:

0.341

Gnomad4 EAS exome

AF:

0.734

Gnomad4 SAS exome

AF:

0.335

Gnomad4 FIN exome

AF:

0.389

Gnomad4 NFE exome

AF:

0.380

Gnomad4 OTH exome

AF:

0.412

GnomAD4 genome

AF:

0.463

AC:

70434

AN:

151976

Hom.:

17251

Cov.:

AF XY:

0.464

AC XY:

34479

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.600

Gnomad4 AMR

AF:

0.480

Gnomad4 ASJ

AF:

0.324

Gnomad4 EAS

AF:

0.711

Gnomad4 SAS

AF:

0.334

Gnomad4 FIN

AF:

0.403

Gnomad4 NFE

AF:

0.385

Gnomad4 OTH

AF:

0.443

Alfa

AF:

0.408

Hom.:

2809

Bravo

AF:

0.482

TwinsUK

AF:

0.372

AC:

1378

ALSPAC

AF:

0.367

AC:

1416

ESP6500AA

AF:

0.504

AC:

1463

ESP6500EA

AF:

0.346

AC:

2172

ExAC

AF:

0.283

AC:

17053

Asia WGS

AF:

0.501

AC:

1719

AN:

3442

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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	Feb 17, 2014	- -

Nemaline myopathy 6

Benign:4

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 13, 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	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0000052

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.0011

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.0

REVEL

Benign

0.14

Sift

Benign

0.30

Sift4G

Pathogenic

0.0

Polyphen

0.89

Vest4

0.24

MPC

1.5

ClinPred

0.031

GERP RS

4.6

Varity_R

0.20

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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