dbSNP rs368781046: KBTBD13:p.Thr318Thr (chr15-65077769-C-G) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001101362.3(KBTBD13):c.954C>G(p.Thr318Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 1,580,356 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T318T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0039 ( 2 hom., cov: 34)

Exomes 𝑓: 0.0034 ( 23 hom. )

Consequence

KBTBD13
NM_001101362.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.73

Publications

1 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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 15-65077769-C-G is Benign according to our data. Variant chr15-65077769-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 129312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.73 with no splicing effect.

BS2

High AC in GnomAd4 at 601 AD,Unknown gene.

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.954C>G	p.Thr318Thr	synonymous	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.954C>G	p.Thr318Thr	synonymous	Exon 1 of 1	ENSP00000388723.2	C9JR72

Frequencies

GnomAD3 genomes

AF:

0.00394

AC:

600

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0100

Gnomad ASJ

AF:

0.0325

Gnomad EAS

AF:

0.0106

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00309

Gnomad OTH

AF:

0.00907

GnomAD2 exomes

AF:

0.00551

AC:

1013

AN:

183844

AF XY:

0.00525

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00704

Gnomad ASJ exome

AF:

0.0305

Gnomad EAS exome

AF:

0.0102

Gnomad FIN exome

AF:

0.0000923

Gnomad NFE exome

AF:

0.00319

Gnomad OTH exome

AF:

0.00679

GnomAD4 exome

AF:

0.00341

AC:

4874

AN:

1428014

Hom.:

Cov.:

AF XY:

0.00354

AC XY:

2508

AN XY:

708876

show subpopulations

African (AFR)

AF:

0.000609

AC:

AN:

32834

American (AMR)

AF:

0.00697

AC:

285

AN:

40872

Ashkenazi Jewish (ASJ)

AF:

0.0302

AC:

776

AN:

25694

East Asian (EAS)

AF:

0.00836

AC:

317

AN:

37938

South Asian (SAS)

AF:

0.00408

AC:

340

AN:

83434

European-Finnish (FIN)

AF:

0.000170

AC:

AN:

41124

Middle Eastern (MID)

AF:

0.00806

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.00247

AC:

2716

AN:

1101090

Other (OTH)

AF:

0.00619

AC:

367

AN:

59322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

344

688

1032

1376

1720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

122

244

366

488

610

<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:

0.00395

AC:

601

AN:

152342

Hom.:

Cov.:

AF XY:

0.00440

AC XY:

328

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.000505

AC:

AN:

41580

American (AMR)

AF:

0.00999

AC:

153

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0325

AC:

113

AN:

3472

East Asian (EAS)

AF:

0.0108

AC:

AN:

5180

South Asian (SAS)

AF:

0.00517

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00309

AC:

210

AN:

68018

Other (OTH)

AF:

0.00899

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

127

159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00449

Hom.:

Bravo

AF:

0.00465

Asia WGS

AF:

0.00376

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Nemaline myopathy 6 (2)

not provided (2)

KBTBD13-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.2

(source)

DANN

Benign

0.70

PhyloP100

-2.7

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over