rs550537101

Variant names:

• chr15-65077029-C-T
• rs550537101
• NM_001101362.3:c.214C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-65077029-C-T
• chr15-65077029-C-G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001101362.3(KBTBD13):​c.214C>T​(p.Leu72Leu) 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
• Publications: 1 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 -16 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 Benign/Likely_benign. ClinVar VariationId is 257454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 290 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.214C>T	p.Leu72Leu	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.214C>T	p.Leu72Leu	synonymous	Exon 1 of 1	ENSP00000388723.2	C9JR72

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

GnomAD2 exomes AF: 0.000316 AC: 33 AN: 104494 AF XY: 0.000309

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 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

African (AFR) AF: 0.00744 AC: 213 AN: 28640

American (AMR) AF: 0.000555 AC: 17 AN: 30640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23588

East Asian (EAS) AF: 0.00 AC: 0 AN: 34146

South Asian (SAS) AF: 0.0000538 AC: 4 AN: 74290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35360

Middle Eastern (MID) AF: 0.000596 AC: 3 AN: 5032

European-Non Finnish (NFE) AF: 0.0000576 AC: 61 AN: 1059158

Other (OTH) AF: 0.000481 AC: 27 AN: 56084

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

African (AFR) AF: 0.00621 AC: 258 AN: 41562

American (AMR) AF: 0.00131 AC: 20 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67970

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.00132 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	12
DANN	Benign	0.89
PhyloP100		3.9
PromoterAI		0.0021	Neutral
Mutation Taster		=95/5	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

Other links and lift over

dbSNP: rs550537101; hg19: chr15-65369367;