chr6-121333450-A-G

Variant names:

• chr6-121333450-A-G
• rs9320808
• NM_152730.6:c.155+826T>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.155+826T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,026 control chromosomes in the GnomAD database, including 37,009 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 0.64 (37009 hom., cov: 31)
• Consequence: TBC1D32 NM_152730.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360
• Publications: 6 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D32	NM_152730.6	c.155+826T>C		intron_variant	Intron 1 of 31	ENST00000398212.7	NP_689943.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D32	ENST00000398212.7	c.155+826T>C		intron_variant	Intron 1 of 31	5	NM_152730.6	ENSP00000381270.2
TBC1D32	ENST00000275159.11	c.155+826T>C		intron_variant	Intron 1 of 32	5		ENSP00000275159.6
TBC1D32	ENST00000464622.5	n.155+826T>C		intron_variant	Intron 1 of 35	2		ENSP00000428839.1
TBC1D32	ENST00000422369.1	c.155+826T>C		intron_variant	Intron 2 of 5	3		ENSP00000397993.1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97854 AN: 151908 Hom.: 37012 Cov.: 31

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.881

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.833

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.793

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.677

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

GnomAD4 genome AF: 0.644 AC: 97857 AN: 152026 Hom.: 37009 Cov.: 31 AF XY: 0.645 AC XY: 47920 AN XY: 74326

African (AFR) AF: 0.238 AC: 9870 AN: 41460

American (AMR) AF: 0.561 AC: 8565 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.833 AC: 2890 AN: 3468

East Asian (EAS) AF: 0.687 AC: 3530 AN: 5142

South Asian (SAS) AF: 0.809 AC: 3897 AN: 4818

European-Finnish (FIN) AF: 0.866 AC: 9154 AN: 10568

Middle Eastern (MID) AF: 0.791 AC: 231 AN: 292

European-Non Finnish (NFE) AF: 0.846 AC: 57495 AN: 67990

Other (OTH) AF: 0.677 AC: 1423 AN: 2102

Alfa AF: 0.789 Hom.: 25033

Bravo AF: 0.599

Asia WGS AF: 0.677 AC: 2356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.0
DANN	Benign	0.79
PhyloP100		0.36
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: rs9320808; hg19: chr6-121654596;