15-65076803-C-T

Position:

• chr15-65076803-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001101362.3(KBTBD13):​c.-13C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00985 in 1,509,882 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0076 (4 hom., cov: 33)
  • Exomes 𝑓: 0.010 (80 hom.)
• Consequence: KBTBD13 NM_001101362.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.262

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 15-65076803-C-T is Benign according to our data. Variant chr15-65076803-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 257449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00757 (1154/152356) while in subpopulation NFE AF= 0.0122 (829/68030). AF 95% confidence interval is 0.0115. There are 4 homozygotes in gnomad4. There are 494 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1154 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KBTBD13	NM_001101362.3	c.-13C>T		5_prime_UTR_premature_start_codon_gain_variant	1/1	ENST00000432196.5	NP_001094832.1
KBTBD13	NM_001101362.3	c.-13C>T		5_prime_UTR_variant	1/1	ENST00000432196.5	NP_001094832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KBTBD13	ENST00000432196	c.-13C>T		5_prime_UTR_premature_start_codon_gain_variant	1/1		NM_001101362.3	ENSP00000388723.2
KBTBD13	ENST00000432196	c.-13C>T		5_prime_UTR_variant	1/1		NM_001101362.3	ENSP00000388723.2

Frequencies

GnomAD3 genomes AF: 0.00758 AC: 1154 AN: 152238 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00471

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00640

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00829 AC: 1062 AN: 128158 Hom.: 8 AF XY: 0.00859 AC XY: 602 AN XY: 70054

Gnomad AFR exome AF: 0.00164

Gnomad AMR exome AF: 0.00329

Gnomad ASJ exome AF: 0.0243

Gnomad EAS exome AF: 0.0000902

Gnomad SAS exome AF: 0.00445

Gnomad FIN exome AF: 0.00878

Gnomad NFE exome AF: 0.0123

Gnomad OTH exome AF: 0.0111

GnomAD4 exome AF: 0.0101 AC: 13725 AN: 1357526 Hom.: 80 Cov.: 28 AF XY: 0.00996 AC XY: 6630 AN XY: 665610

Gnomad4 AFR exome AF: 0.00152

Gnomad4 AMR exome AF: 0.00352

Gnomad4 ASJ exome AF: 0.0216

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00499

Gnomad4 FIN exome AF: 0.00798

Gnomad4 NFE exome AF: 0.0111

Gnomad4 OTH exome AF: 0.00937

GnomAD4 genome AF: 0.00757 AC: 1154 AN: 152356 Hom.: 4 Cov.: 33 AF XY: 0.00663 AC XY: 494 AN XY: 74508

Gnomad4 AFR AF: 0.00216

Gnomad4 AMR AF: 0.00470

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.00640

Gnomad4 NFE AF: 0.0122

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00696 Hom.: 2

Bravo AF: 0.00730

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 07, 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, Dominant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs147079462; hg19: chr15-65369141;