rs201466173

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001101362.3(KBTBD13):c.361G>A(p.Val121Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 1,504,322 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V121L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0039 ( 19 hom. )

Consequence

KBTBD13
NM_001101362.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.43

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

nemaline myopathy 6
Inheritance: AD, Unknown Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P
childhood-onset nemaline myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KBTBD13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073600113).

BP6

Variant 15-65077176-G-A is Benign according to our data. Variant chr15-65077176-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 316740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 331 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KBTBD13	NM_001101362.3 link	c.361G>A	p.Val121Met	missense_variant	Exon 1 of 1	ENST00000432196.5	NP_001094832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KBTBD13	ENST00000432196.5 link	c.361G>A	p.Val121Met	missense_variant	Exon 1 of 1	6	NM_001101362.3	ENSP00000388723.2

Frequencies

GnomAD3 genomes

AF:

0.00218

AC:

332

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.000918

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00402

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.00189

AC:

200

AN:

105916

AF XY:

0.00183

show subpopulations

Gnomad AFR exome

AF:

0.000403

Gnomad AMR exome

AF:

0.000633

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000188

Gnomad NFE exome

AF:

0.00411

Gnomad OTH exome

AF:

0.000924

GnomAD4 exome

AF:

0.00388

AC:

5249

AN:

1352244

Hom.:

Cov.:

AF XY:

0.00385

AC XY:

2565

AN XY:

666232

show subpopulations

African (AFR)

AF:

0.000428

AC:

AN:

28040

American (AMR)

AF:

0.000932

AC:

AN:

32202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24026

East Asian (EAS)

AF:

0.000302

AC:

AN:

33090

South Asian (SAS)

AF:

0.00120

AC:

AN:

76022

European-Finnish (FIN)

AF:

0.000208

AC:

AN:

33578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5454

European-Non Finnish (NFE)

AF:

0.00465

AC:

4950

AN:

1063632

Other (OTH)

AF:

0.00265

AC:

149

AN:

56200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

318

636

954

1272

1590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

392

588

784

980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00218

AC:

331

AN:

152078

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

135

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.000795

AC:

AN:

41524

American (AMR)

AF:

0.000917

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000621

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000284

AC:

AN:

10546

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00402

AC:

273

AN:

67950

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00390

Hom.:

Bravo

AF:

0.00220

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.00128

AC:

ESP6500EA

AF:

0.00342

AC:

ExAC

AF:

0.000720

AC:

Asia WGS

AF:

0.000291

AC:

AN:

3452

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KBTBD13: BS2 -

Oct 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nemaline myopathy 6

Benign:2

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

KBTBD13-related disorder

Benign:1

Jan 10, 2023

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.024

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.55

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.0074

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.6

PhyloP100

2.4

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.21

REVEL

Benign

0.25

Sift

Uncertain

0.020

Sift4G

Uncertain

0.025

Polyphen

0.90

Vest4

0.35

MVP

0.54

MPC

0.74

ClinPred

0.017

GERP RS

1.2

PromoterAI

-0.042

Neutral

(source)

Varity_R

0.067

gMVP

0.50

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over