15-65077062-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4BP6_ModerateBS1BS2

The NM_001101362.3(KBTBD13):ā€‹c.247G>Cā€‹(p.Glu83Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000238 in 1,512,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.00016 ( 0 hom., cov: 34)
Exomes š‘“: 0.00025 ( 0 hom. )

Consequence

KBTBD13
NM_001101362.3 missense

Scores

1
6
12

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.79
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.32861188).
BP6
Variant 15-65077062-G-C is Benign according to our data. Variant chr15-65077062-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 464350.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-65077062-G-C is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000246 (335/1360594) while in subpopulation NFE AF= 0.000304 (324/1064930). AF 95% confidence interval is 0.000276. There are 0 homozygotes in gnomad4_exome. There are 151 alleles in male gnomad4_exome subpopulation. Median coverage is 59. This position pass quality control queck.
BS2
High AC in GnomAd4 at 25 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KBTBD13NM_001101362.3 linkuse as main transcriptc.247G>C p.Glu83Gln missense_variant 1/1 ENST00000432196.5 NP_001094832.1 C9JR72

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KBTBD13ENST00000432196.5 linkuse as main transcriptc.247G>C p.Glu83Gln missense_variant 1/16 NM_001101362.3 ENSP00000388723.2 C9JR72

Frequencies

GnomAD3 genomes
AF:
0.000164
AC:
25
AN:
152076
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000946
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000324
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000112
AC:
13
AN:
116232
Hom.:
0
AF XY:
0.0000775
AC XY:
5
AN XY:
64500
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000457
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000254
Gnomad OTH exome
AF:
0.000280
GnomAD4 exome
AF:
0.000246
AC:
335
AN:
1360594
Hom.:
0
Cov.:
59
AF XY:
0.000225
AC XY:
151
AN XY:
671246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000344
Gnomad4 AMR exome
AF:
0.0000304
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000823
Gnomad4 NFE exome
AF:
0.000304
Gnomad4 OTH exome
AF:
0.000106
GnomAD4 genome
AF:
0.000164
AC:
25
AN:
152184
Hom.:
0
Cov.:
34
AF XY:
0.000161
AC XY:
12
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000946
Gnomad4 NFE
AF:
0.000324
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000152
Hom.:
0
Bravo
AF:
0.000155
ExAC
AF:
0.0000978
AC:
7

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Nemaline myopathy 6 Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.37
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.27
T
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.84
T
M_CAP
Uncertain
0.094
D
MetaRNN
Benign
0.33
T
MetaSVM
Benign
-0.47
T
MutationAssessor
Uncertain
2.6
M
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.13
Sift
Benign
0.073
T
Sift4G
Benign
0.12
T
Polyphen
0.95
P
Vest4
0.26
MutPred
0.39
Gain of helix (P = 0.132);
MVP
0.62
MPC
1.0
ClinPred
0.39
T
GERP RS
3.7
Varity_R
0.26
gMVP
0.52

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.

Other links and lift over

dbSNP: rs781438362; hg19: chr15-65369400; API