rs1399367095

Variant names:

• chr15-65077753-G-T
• rs1399367095
• NM_001101362.3:c.938G>T
• KBTBD13 p.Arg313Leu

Your query was ambiguous. Multiple possible variants found:

• chr15-65077753-G-T
• chr15-65077753-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001101362.3(KBTBD13):​c.938G>T​(p.Arg313Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000281 in 1,424,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R313W) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: KBTBD13 NM_001101362.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28962034).

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.938G>T	p.Arg313Leu	missense	Exon 1 of 1	NP_001094832.1	C9JR72

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KBTBD13	ENST00000432196.5	TSL:6 MANE Select	c.938G>T	p.Arg313Leu	missense	Exon 1 of 1	ENSP00000388723.2	C9JR72

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000111 AC: 2 AN: 179522 AF XY: 0.00000995

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000260

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000281 AC: 4 AN: 1424492 Hom.: 0 Cov.: 84 AF XY: 0.00000424 AC XY: 3 AN XY: 706950

African (AFR) AF: 0.00 AC: 0 AN: 32714

American (AMR) AF: 0.00 AC: 0 AN: 40492

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 37680

South Asian (SAS) AF: 0.00 AC: 0 AN: 83348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 0.00000364 AC: 4 AN: 1099632

Other (OTH) AF: 0.00 AC: 0 AN: 59176

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Nemaline myopathy 6 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.9
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.19
Sift	Benign	0.040	D
Sift4G	Benign	0.10	T
Varity_R		0.20
gMVP		0.53
Mutation Taster		=78/22	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1399367095;

hg19: chr15-65370091;