chr15-65078012-C-T

Variant names:

• chr15-65078012-C-T
• rs150830358
• NM_001101362.3:c.1197C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_001101362.3(KBTBD13):​c.1197C>T​(p.Arg399Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,607,256 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (13 hom., cov: 34)
  • Exomes 𝑓: 0.013 (137 hom.)
• Consequence: KBTBD13 NM_001101362.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.01

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 -12 ACMG points.

• BP6: Variant 15-65078012-C-T is Benign according to our data. Variant chr15-65078012-C-T is described in ClinVar as [Benign]. Clinvar id is 129306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 1581 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KBTBD13	NM_001101362.3	c.1197C>T	p.Arg399Arg	synonymous_variant	Exon 1 of 1	ENST00000432196.5	NP_001094832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KBTBD13	ENST00000432196.5	c.1197C>T	p.Arg399Arg	synonymous_variant	Exon 1 of 1	6	NM_001101362.3	ENSP00000388723.2

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1580 AN: 152198 Hom.: 13 Cov.: 34

Gnomad AFR AF: 0.00275

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.0342

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0137

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.0106 AC: 2495 AN: 235428 Hom.: 30 AF XY: 0.0108 AC XY: 1405 AN XY: 129948

Gnomad AFR exome AF: 0.00216

Gnomad AMR exome AF: 0.00325

Gnomad ASJ exome AF: 0.0148

Gnomad EAS exome AF: 0.0000564

Gnomad SAS exome AF: 0.00202

Gnomad FIN exome AF: 0.0311

Gnomad NFE exome AF: 0.0147

Gnomad OTH exome AF: 0.0102

GnomAD4 exome AF: 0.0127 AC: 18541 AN: 1454940 Hom.: 137 Cov.: 83 AF XY: 0.0125 AC XY: 9037 AN XY: 724128

Gnomad4 AFR exome AF: 0.00143

Gnomad4 AMR exome AF: 0.00352

Gnomad4 ASJ exome AF: 0.0151

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00220

Gnomad4 FIN exome AF: 0.0256

Gnomad4 NFE exome AF: 0.0143

Gnomad4 OTH exome AF: 0.0106

GnomAD4 genome AF: 0.0104 AC: 1581 AN: 152316 Hom.: 13 Cov.: 34 AF XY: 0.0110 AC XY: 822 AN XY: 74466

Gnomad4 AFR AF: 0.00274

Gnomad4 AMR AF: 0.00373

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.0342

Gnomad4 NFE AF: 0.0137

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.0122 Hom.: 2

Bravo AF: 0.00806

Asia WGS AF: 0.00895 AC: 32 AN: 3478

EpiCase AF: 0.0121

EpiControl AF: 0.0124

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 15, 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. -

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 06, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KBTBD13: BS1, BS2 -

Nemaline myopathy 6 Benign:2

Feb 03, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.23		Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs150830358; hg19: chr15-65370350;