rs778682102

Variant names:

• chr15-65077715-C-A
• rs778682102
• NM_001101362.3:c.900C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-65077715-C-A
• chr15-65077715-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001101362.3(KBTBD13):​c.900C>A​(p.Cys300*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. C300C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KBTBD13 NM_001101362.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.557
• 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]

KBTBD13 Gene-Disease associations (from GenCC):

• nemaline myopathy 6

  Inheritance: AD, Unknown Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P
• childhood-onset nemaline myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KBTBD13	NM_001101362.3	MANE Select	c.900C>A	p.Cys300*	stop_gained	Exon 1 of 1	NP_001094832.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KBTBD13	ENST00000432196.5	TSL:6 MANE Select	c.900C>A	p.Cys300*	stop_gained	Exon 1 of 1	ENSP00000388723.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1433490 Hom.: 0 Cov.: 83 AF XY: 0.00 AC XY: 0 AN XY: 711612

African (AFR) AF: 0.00 AC: 0 AN: 32996

American (AMR) AF: 0.00 AC: 0 AN: 42872

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25712

East Asian (EAS) AF: 0.00 AC: 0 AN: 38778

South Asian (SAS) AF: 0.00 AC: 0 AN: 84382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40942

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5584

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102824

Other (OTH) AF: 0.00 AC: 0 AN: 59400

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	34
DANN	Uncertain	0.99
Eigen	Uncertain	0.33
Eigen_PC	Benign	0.018
FATHMM_MKL	Benign	0.59	D
PhyloP100		-0.56
Vest4		0.074
GERP RS		0.62
Mutation Taster		=17/183	disease causing

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

Other links and lift over

dbSNP: rs778682102; hg19: chr15-65370053;