rs184130258

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.981C>G(p.Thr327Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000174 in 1,593,792 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00096 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000091 ( 1 hom. )

Consequence

KBTBD13
NM_001101362.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -5.05

Publications

0 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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 15-65077796-C-G is Benign according to our data. Variant chr15-65077796-C-G is described in ClinVar as Benign. ClinVar VariationId is 316749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.05 with no splicing effect.

BS2

High AC in GnomAd4 at 146 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KBTBD13	NM_001101362.3 link	c.981C>G	p.Thr327Thr	synonymous_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.981C>G	p.Thr327Thr	synonymous_variant	Exon 1 of 1	6	NM_001101362.3	ENSP00000388723.2

Frequencies

GnomAD3 genomes

AF:

0.000942

AC:

143

AN:

151866

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00331

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.000283

AC:

AN:

204992

AF XY:

0.000227

show subpopulations

Gnomad AFR exome

AF:

0.00439

Gnomad AMR exome

AF:

0.000283

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000909

AC:

131

AN:

1441808

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

716626

show subpopulations

African (AFR)

AF:

0.00323

AC:

107

AN:

33166

American (AMR)

AF:

0.000233

AC:

AN:

42834

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25792

East Asian (EAS)

AF:

0.00

AC:

AN:

38920

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84436

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44278

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106794

Other (OTH)

AF:

0.000201

AC:

AN:

59840

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000961

AC:

146

AN:

151984

Hom.:

Cov.:

AF XY:

0.000862

AC XY:

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.00337

AC:

140

AN:

41496

American (AMR)

AF:

0.000262

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5106

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67910

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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:

0.000521

Hom.:

Bravo

AF:

0.00110

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nemaline myopathy 6

Benign:2

Nov 06, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: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. -

not provided

Benign:2

Jan 30, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KBTBD13: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.099

(source)

DANN

Benign

0.48

PhyloP100

-5.0

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over