rs2919358

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A81A) has been classified as Likely 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

Publications

24 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, ClinGen, Labcorp Genetics (formerly Invitae), 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 -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 VariationId is 129308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101362.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KBTBD13	NM_001101362.3	MANE Select	c.242C>T	p.Ala81Val	missense	Exon 1 of 1	NP_001094832.1	C9JR72

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KBTBD13	ENST00000432196.5	TSL:6 MANE Select	c.242C>T	p.Ala81Val	missense	Exon 1 of 1	ENSP00000388723.2	C9JR72

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

GnomAD2 exomes

AF:

0.451

AC:

52069

AN:

115552

AF XY:

0.435

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 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

African (AFR)

AF:

0.612

AC:

17959

AN:

29348

American (AMR)

AF:

0.527

AC:

17397

AN:

33016

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

8275

AN:

24262

East Asian (EAS)

AF:

0.734

AC:

25251

AN:

34390

South Asian (SAS)

AF:

0.335

AC:

25641

AN:

76510

European-Finnish (FIN)

AF:

0.389

AC:

14147

AN:

36408

Middle Eastern (MID)

AF:

0.373

AC:

2002

AN:

5374

European-Non Finnish (NFE)

AF:

0.380

AC:

406136

AN:

1068906

Other (OTH)

AF:

0.412

AC:

23381

AN:

56724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

18323

36646

54970

73293

91616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13052

26104

39156

52208

65260

<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:

0.463

AC:

70434

AN:

151976

Hom.:

17251

Cov.:

AF XY:

0.464

AC XY:

34479

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.600

AC:

24907

AN:

41502

American (AMR)

AF:

0.480

AC:

7339

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.324

AC:

1123

AN:

3464

East Asian (EAS)

AF:

0.711

AC:

3669

AN:

5158

South Asian (SAS)

AF:

0.334

AC:

1613

AN:

4832

European-Finnish (FIN)

AF:

0.403

AC:

4255

AN:

10554

Middle Eastern (MID)

AF:

0.438

AC:

128

AN:

292

European-Non Finnish (NFE)

AF:

0.385

AC:

26113

AN:

67880

Other (OTH)

AF:

0.443

AC:

934

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1952

3904

5855

7807

9759

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

628

1256

1884

2512

3140

<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:

0.428

Hom.:

5604

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Nemaline myopathy 6 (4)

not specified (4)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

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

PhyloP100

7.6

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

PromoterAI

-0.033

Neutral

(source)

Varity_R

0.20

gMVP

0.50

Mutation Taster

=75/25

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over