NM_001101362.3:c.64C>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001101362.3(KBTBD13):c.64C>G(p.Arg22Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000703 in 1,564,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R22C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

KBTBD13
NM_001101362.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 2.13

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 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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.901

BS2

High AC in GnomAdExome4 at 10 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.64C>G	p.Arg22Gly	missense	Exon 1 of 1	NP_001094832.1	C9JR72
	RASL12	NM_001379429.1		c.-281G>C		upstream_gene	N/A	NP_001366358.1	Q9NYN1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KBTBD13	ENST00000432196.5	TSL:6 MANE Select	c.64C>G	p.Arg22Gly	missense	Exon 1 of 1	ENSP00000388723.2	C9JR72
	RASL12	ENST00000434605.2	TSL:2	c.-281G>C		upstream_gene	N/A	ENSP00000412787.2	Q9NYN1-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000170

AC:

AN:

176442

AF XY:

0.0000207

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000260

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000708

AC:

AN:

1412526

Hom.:

Cov.:

AF XY:

0.0000100

AC XY:

AN XY:

699850

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32710

American (AMR)

AF:

0.0000250

AC:

AN:

40042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25532

East Asian (EAS)

AF:

0.00

AC:

AN:

37722

South Asian (SAS)

AF:

0.00

AC:

AN:

80950

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37518

Middle Eastern (MID)

AF:

0.000233

AC:

AN:

4284

European-Non Finnish (NFE)

AF:

0.00000639

AC:

AN:

1094944

Other (OTH)

AF:

0.0000170

AC:

AN:

58824

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2092

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

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:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Nemaline myopathy 6 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

0.00058

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Uncertain

0.72

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.90

MetaSVM

Benign

-0.45

MutationAssessor

Uncertain

2.5

PhyloP100

2.1

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-4.1

REVEL

Uncertain

0.39

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.012

Polyphen

0.55

Vest4

0.36

MutPred

0.84

Loss of helix (P = 0.1299)

MVP

0.59

MPC

1.1

ClinPred

0.39

GERP RS

3.4

PromoterAI

0.0028

Neutral

(source)

Varity_R

0.58

gMVP

0.58

Mutation Taster

=64/36

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

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