15-65077029-C-T

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.214C>T(p.Leu72=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00041 in 1,499,150 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00024 (3 hom.)
• Consequence: KBTBD13 NM_001101362.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.87

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 (BayesDel_noAF=-0.47).
• BP6: Variant 15-65077029-C-T is Benign according to our data. Variant chr15-65077029-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 257454.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 = 0.00191 (290/152212) while in subpopulation AFR AF= 0.00621 (258/41562). AF 95% confidence interval is 0.00559. There are 1 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 GnomAd at 290 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KBTBD13	NM_001101362.3	c.214C>T	p.Leu72=	synonymous_variant	1/1	ENST00000432196.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KBTBD13	ENST00000432196.5	c.214C>T	p.Leu72=	synonymous_variant	1/1		NM_001101362.3	P1

Frequencies

GnomAD3 genomes AF: 0.00191 AC: 290 AN: 152104 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00623

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

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: 0.0000736

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.000316 AC: 33 AN: 104494 Hom.: 0 AF XY: 0.000309 AC XY: 18 AN XY: 58162

Gnomad AFR exome AF: 0.00446

Gnomad AMR exome AF: 0.000575

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000581

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000752

Gnomad OTH exome AF: 0.000610

GnomAD4 exome AF: 0.000241 AC: 325 AN: 1346938 Hom.: 3 Cov.: 29 AF XY: 0.000219 AC XY: 145 AN XY: 662940

Gnomad4 AFR exome AF: 0.00744

Gnomad4 AMR exome AF: 0.000555

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000538

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000576

Gnomad4 OTH exome AF: 0.000481

GnomAD4 genome AF: 0.00191 AC: 290 AN: 152212 Hom.: 1 Cov.: 33 AF XY: 0.00184 AC XY: 137 AN XY: 74440

Gnomad4 AFR AF: 0.00621

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000736

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00132 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Nemaline myopathy 6 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 13, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	12
Dann	Benign	0.89

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: rs550537101; hg19: chr15-65369367;