rs561115735

Variant names:

• chr15-65076840-G-T
• rs561115735
• NM_001101362.3:c.25G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-65076840-G-T
• chr15-65076840-G-A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001101362.3(KBTBD13):​c.25G>T​(p.Val9Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000045 in 1,555,630 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 (★★). Synonymous variant affecting the same amino acid position (i.e. V9V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KBTBD13 NM_001101362.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 1.38
• 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]

RASL12 (HGNC:30289): (RAS like family 12) Predicted to enable GDP binding activity; GTP binding activity; and GTPase activity. Predicted to be involved in signal transduction. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3618658).
• BS2: High AC in GnomAd4 at 5 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.25G>T	p.Val9Leu	missense	Exon 1 of 1	NP_001094832.1	C9JR72
	RASL12	NM_001379429.1		c.-242C>A		upstream_gene	N/A	NP_001366358.1	Q9NYN1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KBTBD13	ENST00000432196.5	TSL:6 MANE Select	c.25G>T	p.Val9Leu	missense	Exon 1 of 1	ENSP00000388723.2	C9JR72
	RASL12	ENST00000434605.2	TSL:2	c.-242C>A		upstream_gene	N/A	ENSP00000412787.2	Q9NYN1-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1403268 Hom.: 0 Cov.: 29 AF XY: 0.00000144 AC XY: 1 AN XY: 693968

African (AFR) AF: 0.0000616 AC: 2 AN: 32482

American (AMR) AF: 0.00 AC: 0 AN: 39150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25404

East Asian (EAS) AF: 0.00 AC: 0 AN: 37268

South Asian (SAS) AF: 0.00 AC: 0 AN: 80408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4360

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1089392

Other (OTH) AF: 0.00 AC: 0 AN: 58370

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152362 Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4 AN XY: 74506

African (AFR) AF: 0.000120 AC: 5 AN: 41582

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	Nemaline myopathy 6 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	0.0053	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.51	N
PhyloP100		1.4
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.38
Sift	Benign	0.10	T
Sift4G	Benign	0.15	T
Polyphen		0.22	B
Vest4		0.44
MutPred		0.61		Loss of MoRF binding (P = 0.1087)
MVP		0.56
MPC		0.53
ClinPred		0.12	T
GERP RS		3.5
PromoterAI		0.015	Neutral
Varity_R		0.24
gMVP		0.50
Mutation Taster		=89/11	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: rs561115735; hg19: chr15-65369178;