rs17083119

Variant names:

• chr6-121080964-A-G
• rs17083119
• NM_152730.6:c.3655-74T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

TBC1D32 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE, MODERATE Submitted by: Illumina, G2P
• orofaciodigital syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox
• orofaciodigital syndrome IX

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TBC1D32	NM_152730.6	c.3655-74T>C		intron_variant	Intron 31 of 31	ENST00000398212.7	NP_689943.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D32	ENST00000398212.7	c.3655-74T>C		intron_variant	Intron 31 of 31	5	NM_152730.6	ENSP00000381270.2
TBC1D32	ENST00000275159.11	c.3778-74T>C		intron_variant	Intron 32 of 32	5		ENSP00000275159.6
TBC1D32	ENST00000464622.5	n.*4295-74T>C		intron_variant	Intron 35 of 35	2		ENSP00000428839.1

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

African (AFR) AF: 0.223 AC: 6936 AN: 31150

American (AMR) AF: 0.0204 AC: 745 AN: 36580

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 225 AN: 22292

East Asian (EAS) AF: 0.0783 AC: 3044 AN: 38854

South Asian (SAS) AF: 0.0471 AC: 3539 AN: 75124

European-Finnish (FIN) AF: 0.000393 AC: 20 AN: 50930

Middle Eastern (MID) AF: 0.0350 AC: 190 AN: 5428

European-Non Finnish (NFE) AF: 0.00308 AC: 3295 AN: 1068346

Other (OTH) AF: 0.0257 AC: 1475 AN: 57374

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

African (AFR) AF: 0.210 AC: 8733 AN: 41504

American (AMR) AF: 0.0293 AC: 449 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3470

East Asian (EAS) AF: 0.0862 AC: 447 AN: 5188

South Asian (SAS) AF: 0.0537 AC: 259 AN: 4820

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.00375 AC: 255 AN: 68014

Other (OTH) AF: 0.0605 AC: 128 AN: 2116

Alfa AF: 0.0471 Hom.: 92

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
PhyloP100		-0.54
Mutation Taster		=100/0	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: rs17083119; hg19: chr6-121402110;