rs2919359

Variant names:

• chr15-65077613-A-G
• rs2919359
• NM_001101362.3:c.798A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-65077613-A-G
• chr15-65077613-A-C
• chr15-65077613-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001101362.3(KBTBD13):​c.798A>G​(p.Glu266Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 1,583,266 control chromosomes in the GnomAD database, including 584,045 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (57740 hom., cov: 34)
  • Exomes 𝑓: 0.86 (526305 hom.)
• Consequence: KBTBD13 NM_001101362.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 1.49
• Publications: 16 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, ClinGen, Labcorp Genetics (formerly Invitae), G2P
• childhood-onset nemaline myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 15-65077613-A-G is Benign according to our data. Variant chr15-65077613-A-G is described in ClinVar as Benign. ClinVar VariationId is 129311.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.49 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

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.798A>G	p.Glu266Glu	synonymous	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.798A>G	p.Glu266Glu	synonymous	Exon 1 of 1	ENSP00000388723.2	C9JR72

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132338 AN: 152060 Hom.: 57682 Cov.: 34

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.863

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.873

GnomAD2 exomes AF: 0.874 AC: 171772 AN: 196580 AF XY: 0.875

Gnomad AFR exome AF: 0.903

Gnomad AMR exome AF: 0.857

Gnomad ASJ exome AF: 0.863

Gnomad EAS exome AF: 0.984

Gnomad FIN exome AF: 0.832

Gnomad NFE exome AF: 0.854

Gnomad OTH exome AF: 0.859

GnomAD4 exome AF: 0.857 AC: 1226675 AN: 1431088 Hom.: 526305 Cov.: 77 AF XY: 0.858 AC XY: 610365 AN XY: 711046

African (AFR) AF: 0.905 AC: 29744 AN: 32862

American (AMR) AF: 0.857 AC: 36494 AN: 42578

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 22281 AN: 25800

East Asian (EAS) AF: 0.979 AC: 37549 AN: 38366

South Asian (SAS) AF: 0.905 AC: 75883 AN: 83810

European-Finnish (FIN) AF: 0.833 AC: 32458 AN: 38952

Middle Eastern (MID) AF: 0.861 AC: 4915 AN: 5706

European-Non Finnish (NFE) AF: 0.848 AC: 935928 AN: 1103546

Other (OTH) AF: 0.865 AC: 51423 AN: 59468

GnomAD4 genome AF: 0.870 AC: 132455 AN: 152178 Hom.: 57740 Cov.: 34 AF XY: 0.869 AC XY: 64680 AN XY: 74404

African (AFR) AF: 0.903 AC: 37528 AN: 41564

American (AMR) AF: 0.848 AC: 12963 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 2963 AN: 3472

East Asian (EAS) AF: 0.986 AC: 5071 AN: 5142

South Asian (SAS) AF: 0.903 AC: 4360 AN: 4830

European-Finnish (FIN) AF: 0.841 AC: 8926 AN: 10612

Middle Eastern (MID) AF: 0.873 AC: 255 AN: 292

European-Non Finnish (NFE) AF: 0.849 AC: 57693 AN: 67946

Other (OTH) AF: 0.874 AC: 1847 AN: 2114

Alfa AF: 0.856 Hom.: 23298

Bravo AF: 0.875

Asia WGS AF: 0.914 AC: 3169 AN: 3466

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	4	Nemaline myopathy 6 (4)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.2
DANN	Benign	0.52
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs2919359; hg19: chr15-65369951; COSMIC: COSV71351420; COSMIC: COSV71351420;