15-65076930-G-C

Position:

• chr15-65076930-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001101362.3(KBTBD13):​c.115G>C​(p.Gly39Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000401 in 1,557,718 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: KBTBD13 NM_001101362.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 9.63

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014871269).
• BP6: Variant 15-65076930-G-C is Benign according to our data. Variant chr15-65076930-G-C is described in ClinVar as [Benign]. Clinvar id is 377996.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0019 (290/152342) while in subpopulation AFR AF= 0.00628 (261/41582). AF 95% confidence interval is 0.00565. There are 0 homozygotes in gnomad4. There are 137 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 290 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KBTBD13	NM_001101362.3	c.115G>C	p.Gly39Arg	missense_variant	1/1	ENST00000432196.5	NP_001094832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KBTBD13	ENST00000432196.5	c.115G>C	p.Gly39Arg	missense_variant	1/1	6	NM_001101362.3	ENSP00000388723.2

Frequencies

GnomAD3 genomes AF: 0.00191 AC: 290 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00630

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000915

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.000445 AC: 73 AN: 163868 Hom.: 1 AF XY: 0.000311 AC XY: 28 AN XY: 89980

Gnomad AFR exome AF: 0.00572

Gnomad AMR exome AF: 0.000434

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: 0.0000864

Gnomad OTH exome AF: 0.000649

GnomAD4 exome AF: 0.000238 AC: 335 AN: 1405376 Hom.: 0 Cov.: 29 AF XY: 0.000213 AC XY: 148 AN XY: 695912

Gnomad4 AFR exome AF: 0.00677

Gnomad4 AMR exome AF: 0.000460

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000269

Gnomad4 SAS exome AF: 0.0000373

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000568

Gnomad4 OTH exome AF: 0.000495

GnomAD4 genome AF: 0.00190 AC: 290 AN: 152342 Hom.: 0 Cov.: 33 AF XY: 0.00184 AC XY: 137 AN XY: 74498

Gnomad4 AFR AF: 0.00628

Gnomad4 AMR AF: 0.000914

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000170 Hom.: 0

Bravo AF: 0.00206

ESP6500AA AF: 0.00467 AC: 18

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000447 AC: 52

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2016

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. -

Nemaline myopathy 6 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 28, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.63	D
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.015	T
MetaSVM	Uncertain	0.25	D
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.78
MVP		0.67
MPC		1.6
ClinPred		0.060	T
GERP RS		3.7
Varity_R		0.87
gMVP		0.66

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

Other links and lift over

dbSNP: rs201420126; hg19: chr15-65369268;