6-121280619-C-T

Variant names:

• chr6-121280619-C-T
• rs10499102
• NM_152730.6:c.1608+925G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152730.6(TBC1D32):​c.1608+925G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0328 in 151,652 control chromosomes in the GnomAD database, including 192 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 0.033 (192 hom., cov: 32)
• Consequence: TBC1D32 NM_152730.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D32	NM_152730.6	c.1608+925G>A		intron_variant	Intron 14 of 31	ENST00000398212.7	NP_689943.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D32	ENST00000398212.7	c.1608+925G>A		intron_variant	Intron 14 of 31	5	NM_152730.6	ENSP00000381270.2
TBC1D32	ENST00000275159.11	c.1608+925G>A		intron_variant	Intron 14 of 32	5		ENSP00000275159.6
TBC1D32	ENST00000464622.5	n.*1299+925G>A		intron_variant	Intron 14 of 35	2		ENSP00000428839.1

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 4973 AN: 151536 Hom.: 191 Cov.: 32

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0294

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.0332

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0328 AC: 4976 AN: 151652 Hom.: 192 Cov.: 32 AF XY: 0.0351 AC XY: 2599 AN XY: 74104

African (AFR) AF: 0.0348 AC: 1441 AN: 41440

American (AMR) AF: 0.101 AC: 1540 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 38 AN: 3462

East Asian (EAS) AF: 0.119 AC: 612 AN: 5156

South Asian (SAS) AF: 0.0124 AC: 60 AN: 4822

European-Finnish (FIN) AF: 0.0294 AC: 310 AN: 10560

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0133 AC: 901 AN: 67704

Other (OTH) AF: 0.0347 AC: 73 AN: 2102

Alfa AF: 0.0366 Hom.: 37

Bravo AF: 0.0413

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.9
DANN	Benign	0.82
PhyloP100		-0.46
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: rs10499102; hg19: chr6-121601765; COSMIC: COSV51543219;