rs17083119

Positions:

• chr6-121080964-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152730.6(TBC1D32):​c.3655-74T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,538,312 control chromosomes in the GnomAD database, including 2,165 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.068 (1016 hom., cov: 32)
  • Exomes 𝑓: 0.014 (1149 hom.)
• Consequence: TBC1D32 NM_152730.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540

Genes affected

TBC1D32 (HGNC:21485): (TBC1 domain family member 32) This gene encodes a TBC-domain containing protein. Studies of a similar protein in mouse and zebrafish suggest that the encoded protein is involved in sonic hedgehog signaling, and that it interacts with and stabilizes cell cycle-related kinase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D32	NM_152730.6	c.3655-74T>C		intron_variant		ENST00000398212.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D32	ENST00000398212.7	c.3655-74T>C		intron_variant		5	NM_152730.6

Frequencies

GnomAD3 genomes AF: 0.0676 AC: 10287 AN: 152116 Hom.: 1015 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0294

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.0860

Gnomad SAS AF: 0.0531

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00375

Gnomad OTH AF: 0.0606

GnomAD4 exome AF: 0.0140 AC: 19469 AN: 1386078 Hom.: 1149 AF XY: 0.0142 AC XY: 9744 AN XY: 687270

Gnomad4 AFR exome AF: 0.223

Gnomad4 AMR exome AF: 0.0204

Gnomad4 ASJ exome AF: 0.0101

Gnomad4 EAS exome AF: 0.0783

Gnomad4 SAS exome AF: 0.0471

Gnomad4 FIN exome AF: 0.000393

Gnomad4 NFE exome AF: 0.00308

Gnomad4 OTH exome AF: 0.0257

GnomAD4 genome AF: 0.0678 AC: 10320 AN: 152234 Hom.: 1016 Cov.: 32 AF XY: 0.0674 AC XY: 5018 AN XY: 74432

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.0293

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.0862

Gnomad4 SAS AF: 0.0537

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00375

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0400 Hom.: 72

Bravo AF: 0.0768

Asia WGS AF: 0.0940 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.44

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

LitVar

Other links and lift over

dbSNP: rs17083119; hg19: chr6-121402110;