Genetic Variant KBTBD13:p.Leu72Val (chr15-65077029-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001101362.3(KBTBD13):c.214C>G(p.Leu72Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000742 in 1,346,938 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L72L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

KBTBD13
NM_001101362.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.87

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, 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KBTBD13	NM_001101362.3 link	c.214C>G	p.Leu72Val	missense_variant	Exon 1 of 1	ENST00000432196.5	NP_001094832.1	C9JR72

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KBTBD13	ENST00000432196.5 link	c.214C>G	p.Leu72Val	missense_variant	Exon 1 of 1	6	NM_001101362.3	ENSP00000388723.2		C9JR72

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

104494

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

7.42e-7

AC:

AN:

1346938

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

662940

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28640

American (AMR)

AF:

0.00

AC:

AN:

30640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23588

East Asian (EAS)

AF:

0.00

AC:

AN:

34146

South Asian (SAS)

AF:

0.00

AC:

AN:

74290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5032

European-Non Finnish (NFE)

AF:

9.44e-7

AC:

AN:

1059158

Other (OTH)

AF:

0.00

AC:

AN:

56084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.0041

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.15

Eigen

Benign

0.13

Eigen_PC

Benign

0.11

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.52

M_CAP

Benign

0.072

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-0.48

MutationAssessor

Benign

2.0

PhyloP100

3.9

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.93

REVEL

Benign

0.17

Sift

Benign

0.078

Sift4G

Uncertain

0.017

Polyphen

0.91

Vest4

0.56

MutPred

0.37

Loss of helix (P = 0.0626);

MVP

0.67

MPC

1.2

ClinPred

0.46

GERP RS

2.7

PromoterAI

0.0033

Neutral

(source)

Varity_R

0.14

gMVP

0.36

Mutation Taster

=81/19

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over