NM_001101362.3:c.1200T>C

Variant names:

• chr15-65078015-T-C
• rs2919360
• NM_001101362.3:c.1200T>C

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.1200T>C​(p.Gly400Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,606,120 control chromosomes in the GnomAD database, including 798,499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (74770 hom., cov: 36)
  • Exomes 𝑓: 1.0 (723729 hom.)
• Consequence: KBTBD13 NM_001101362.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -4.21
• Publications: 14 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=-0.87).
• BP6: Variant 15-65078015-T-C is Benign according to our data. Variant chr15-65078015-T-C is described in ClinVar as Benign. ClinVar VariationId is 129307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.21 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 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.1200T>C	p.Gly400Gly	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.1200T>C	p.Gly400Gly	synonymous	Exon 1 of 1	ENSP00000388723.2	C9JR72

Frequencies

GnomAD3 genomes AF: 0.991 AC: 150837 AN: 152258 Hom.: 74715 Cov.: 36

Gnomad AFR AF: 0.973

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.993

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.991

GnomAD2 exomes AF: 0.996 AC: 234485 AN: 235450 AF XY: 0.996

Gnomad AFR exome AF: 0.972

Gnomad AMR exome AF: 0.996

Gnomad ASJ exome AF: 0.978

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.998

Gnomad OTH exome AF: 0.996

GnomAD4 exome AF: 0.998 AC: 1450572 AN: 1453744 Hom.: 723729 Cov.: 83 AF XY: 0.998 AC XY: 722027 AN XY: 723550

African (AFR) AF: 0.972 AC: 32525 AN: 33468

American (AMR) AF: 0.995 AC: 44405 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.980 AC: 25560 AN: 26078

East Asian (EAS) AF: 1.00 AC: 39686 AN: 39686

South Asian (SAS) AF: 1.00 AC: 86127 AN: 86130

European-Finnish (FIN) AF: 1.00 AC: 46024 AN: 46034

Middle Eastern (MID) AF: 0.991 AC: 5716 AN: 5766

European-Non Finnish (NFE) AF: 0.999 AC: 1110540 AN: 1111674

Other (OTH) AF: 0.995 AC: 59989 AN: 60294

GnomAD4 genome AF: 0.991 AC: 150951 AN: 152376 Hom.: 74770 Cov.: 36 AF XY: 0.991 AC XY: 73813 AN XY: 74510

African (AFR) AF: 0.973 AC: 40470 AN: 41596

American (AMR) AF: 0.993 AC: 15202 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.976 AC: 3389 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5176 AN: 5176

South Asian (SAS) AF: 1.00 AC: 4833 AN: 4834

European-Finnish (FIN) AF: 1.00 AC: 10629 AN: 10630

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67951 AN: 68036

Other (OTH) AF: 0.991 AC: 2095 AN: 2114

Alfa AF: 0.994 Hom.: 40771

Bravo AF: 0.989

Asia WGS AF: 0.998 AC: 3471 AN: 3478

EpiCase AF: 0.997

EpiControl AF: 0.997

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	Nemaline myopathy 6 (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.62
PhyloP100		-4.2
Mutation Taster		=99/1	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: rs2919360; hg19: chr15-65370353; COSMIC: COSV71351505; COSMIC: COSV71351505;