15-65077208-C-G

Variant names:

• chr15-65077208-C-G
• NM_001101362.3:c.393C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001101362.3(KBTBD13):​c.393C>G​(p.Asp131Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000154 in 1,297,698 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: KBTBD13 NM_001101362.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.662

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KBTBD13	NM_001101362.3	c.393C>G	p.Asp131Glu	missense_variant	Exon 1 of 1	ENST00000432196.5	NP_001094832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KBTBD13	ENST00000432196.5	c.393C>G	p.Asp131Glu	missense_variant	Exon 1 of 1	6	NM_001101362.3	ENSP00000388723.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000154 AC: 2 AN: 1297698 Hom.: 0 Cov.: 40 AF XY: 0.00000158 AC XY: 1 AN XY: 634364

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.66e-7

Gnomad4 OTH exome AF: 0.0000186

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.0099	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.035	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.088
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.46	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.30
Sift	Benign	0.033	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.50
MutPred		0.31		Gain of disorder (P = 0.1851);
MVP		0.66
MPC		1.4
ClinPred		0.87	D
GERP RS		3.6
Varity_R		0.14
gMVP		0.48

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-65369546;