rs138484272

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001101362.3(KBTBD13):c.89G>A(p.Gly30Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0044 in 1,564,574 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0045 ( 47 hom. )

Consequence

KBTBD13
NM_001101362.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.35

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:

RASL12 (HGNC:30289): (RAS like family 12) Predicted to enable GDP binding activity; GTP binding activity; and GTPase activity. Predicted to be involved in signal transduction. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RASL12 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=0.0052545667).

BP6

Variant 15-65076904-G-A is Benign according to our data. Variant chr15-65076904-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-65076904-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00452 (6381/1412236) while in subpopulation MID AF= 0.0209 (90/4296). AF 95% confidence interval is 0.0175. There are 47 homozygotes in gnomad4_exome. There are 3331 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High AC in GnomAd4 at 508 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KBTBD13	NM_001101362.3 link	c.89G>A	p.Gly30Asp	missense_variant	Exon 1 of 1	ENST00000432196.5	NP_001094832.1	C9JR72
RASL12	NM_001379429.1 link	c.-306C>T		upstream_gene_variant			NP_001366358.1
RASL12	XM_011521660.4 link	c.-355C>T		upstream_gene_variant			XP_011519962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KBTBD13	ENST00000432196.5 link	c.89G>A	p.Gly30Asp	missense_variant	Exon 1 of 1	6	NM_001101362.3	ENSP00000388723.2		C9JR72
RASL12	ENST00000434605.2 link	c.-306C>T		upstream_gene_variant		2		ENSP00000412787.2		Q9NYN1-2

Frequencies

GnomAD3 genomes

AF:

0.00333

AC:

507

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00827

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00441

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00581

AC:

1024

AN:

176254

Hom.:

AF XY:

0.00633

AC XY:

613

AN XY:

96786

show subpopulations

Gnomad AFR exome

AF:

0.000599

Gnomad AMR exome

AF:

0.00402

Gnomad ASJ exome

AF:

0.0229

Gnomad EAS exome

AF:

0.0000718

Gnomad SAS exome

AF:

0.0101

Gnomad FIN exome

AF:

0.000488

Gnomad NFE exome

AF:

0.00513

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.00452

AC:

6381

AN:

1412236

Hom.:

Cov.:

AF XY:

0.00476

AC XY:

3331

AN XY:

699736

show subpopulations

Gnomad4 AFR exome

AF:

0.000979

Gnomad4 AMR exome

AF:

0.00439

Gnomad4 ASJ exome

AF:

0.0245

Gnomad4 EAS exome

AF:

0.0000796

Gnomad4 SAS exome

AF:

0.00957

Gnomad4 FIN exome

AF:

0.000615

Gnomad4 NFE exome

AF:

0.00394

Gnomad4 OTH exome

AF:

0.00580

GnomAD4 genome

AF:

0.00333

AC:

508

AN:

152338

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

241

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000721

Gnomad4 AMR

AF:

0.00274

Gnomad4 ASJ

AF:

0.0210

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00849

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00441

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00586

Hom.:

Bravo

AF:

0.00334

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000255

AC:

ESP6500EA

AF:

0.00415

AC:

ExAC

AF:

0.00444

AC:

521

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 26, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nemaline myopathy 6

Benign:2

Jan 29, 2025

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

Breakthrough Genomics, Breakthrough Genomics

Significance: 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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.11

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0053

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.69

PrimateAI

Uncertain

0.67

PROVEAN

Benign

3.2

REVEL

Benign

0.070

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0070

Vest4

0.18

MVP

0.28

MPC

0.70

ClinPred

0.0051

GERP RS

2.6

Varity_R

0.097

gMVP

0.47

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

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