chr15-65076932-C-T

Variant names:

• chr15-65076932-C-T
• rs367684457
• NM_001101362.3:c.117C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001101362.3(KBTBD13):​c.117C>T​(p.Gly39Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,557,390 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00098 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000094 (1 hom.)
• Consequence: KBTBD13 NM_001101362.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.35
• 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 15-65076932-C-T is Benign according to our data. Variant chr15-65076932-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 316734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.35 with no splicing effect.
• BS2: High AC in GnomAd4 at 150 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.117C>T	p.Gly39Gly	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.117C>T	p.Gly39Gly	synonymous	Exon 1 of 1	ENSP00000388723.2	C9JR72
	RASL12	ENST00000434605.2	TSL:2	c.-334G>A		upstream_gene	N/A	ENSP00000412787.2	Q9NYN1-2

Frequencies

GnomAD3 genomes AF: 0.000933 AC: 142 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00328

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.00

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000281 AC: 46 AN: 163470 AF XY: 0.000189

Gnomad AFR exome AF: 0.00407

Gnomad AMR exome AF: 0.000326

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000939 AC: 132 AN: 1405038 Hom.: 1 Cov.: 29 AF XY: 0.0000776 AC XY: 54 AN XY: 695752

African (AFR) AF: 0.00323 AC: 105 AN: 32464

American (AMR) AF: 0.000256 AC: 10 AN: 39022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25416

East Asian (EAS) AF: 0.00 AC: 0 AN: 37228

South Asian (SAS) AF: 0.0000124 AC: 1 AN: 80486

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36410

Middle Eastern (MID) AF: 0.000460 AC: 2 AN: 4352

European-Non Finnish (NFE) AF: 0.00000275 AC: 3 AN: 1091136

Other (OTH) AF: 0.000188 AC: 11 AN: 58524

GnomAD4 genome AF: 0.000985 AC: 150 AN: 152352 Hom.: 0 Cov.: 33 AF XY: 0.000913 AC XY: 68 AN XY: 74504

African (AFR) AF: 0.00346 AC: 144 AN: 41588

American (AMR) AF: 0.000261 AC: 4 AN: 15312

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000513 Hom.: 0

Bravo AF: 0.00110

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Nemaline myopathy 6 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Benign	0.94
PhyloP100		1.4
PromoterAI		0.034	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs367684457; hg19: chr15-65369270;