15-65076803-C-T

Variant names:

• chr15-65076803-C-T
• rs147079462
• NM_001101362.3:c.-13C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong 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
• Publications: 0 publications found

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]

RASL12 (HGNC:30289): (RAS like family 12) Predicted to enable GDP binding activity; GTP binding activity; and GTPase activity. Predicted to be involved in signal transduction. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -14 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 Benign/Likely_benign. ClinVar VariationId is 257449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 1154 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101362.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KBTBD13	NM_001101362.3	MANE Select	c.-13C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 1	NP_001094832.1	C9JR72
	KBTBD13	NM_001101362.3	MANE Select	c.-13C>T		5_prime_UTR	Exon 1 of 1	NP_001094832.1	C9JR72
	RASL12	NM_001379429.1		c.-205G>A		upstream_gene	N/A	NP_001366358.1	Q9NYN1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KBTBD13	ENST00000432196.5	TSL:6 MANE Select	c.-13C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 1	ENSP00000388723.2	C9JR72
	KBTBD13	ENST00000432196.5	TSL:6 MANE Select	c.-13C>T		5_prime_UTR	Exon 1 of 1	ENSP00000388723.2	C9JR72
	RASL12	ENST00000434605.2	TSL:2	c.-205G>A		upstream_gene	N/A	ENSP00000412787.2	Q9NYN1-2

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

GnomAD2 exomes AF: 0.00829 AC: 1062 AN: 128158 AF XY: 0.00859

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 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

African (AFR) AF: 0.00152 AC: 47 AN: 30998

American (AMR) AF: 0.00352 AC: 120 AN: 34046

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 518 AN: 23968

East Asian (EAS) AF: 0.00 AC: 0 AN: 35616

South Asian (SAS) AF: 0.00499 AC: 380 AN: 76134

European-Finnish (FIN) AF: 0.00798 AC: 270 AN: 33838

Middle Eastern (MID) AF: 0.00766 AC: 35 AN: 4572

European-Non Finnish (NFE) AF: 0.0111 AC: 11826 AN: 1061906

Other (OTH) AF: 0.00937 AC: 529 AN: 56448

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

African (AFR) AF: 0.00216 AC: 90 AN: 41586

American (AMR) AF: 0.00470 AC: 72 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 64 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00331 AC: 16 AN: 4830

European-Finnish (FIN) AF: 0.00640 AC: 68 AN: 10628

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0122 AC: 829 AN: 68030

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00696 Hom.: 2

Bravo AF: 0.00730

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Nemaline Myopathy, Dominant (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		0.26
PromoterAI		-0.0052	Neutral

Splicing

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

Other links and lift over

dbSNP: rs147079462; hg19: chr15-65369141;