chr6-121091045-T-TA

Variant names:

• chr6-121091045-T-TA
• rs397887772
• NM_152730.6:c.3466-5dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_152730.6(TBC1D32):​c.3466-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,224,990 control chromosomes in the GnomAD database, including 12,453 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (7362 hom., cov: 23)
  • Exomes 𝑓: 0.19 (5091 hom.)
• Consequence: TBC1D32 NM_152730.6 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.424
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 6-121091045-T-TA is Benign according to our data. Variant chr6-121091045-T-TA is described in ClinVar as [Benign]. Clinvar id is 1560532.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D32	NM_152730.6	c.3466-5dupT		splice_region_variant, intron_variant	Intron 30 of 31	ENST00000398212.7	NP_689943.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D32	ENST00000398212.7	c.3466-5_3466-4insT		splice_region_variant, intron_variant	Intron 30 of 31	5	NM_152730.6	ENSP00000381270.2
TBC1D32	ENST00000275159.11	c.3589-5_3589-4insT		splice_region_variant, intron_variant	Intron 31 of 32	5		ENSP00000275159.6
TBC1D32	ENST00000464622.5	n.*4106-5_*4106-4insT		splice_region_variant, intron_variant	Intron 34 of 35	2		ENSP00000428839.1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 38878 AN: 147826 Hom.: 7341 Cov.: 23

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0987

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.243

GnomAD2 exomes AF: 0.255 AC: 34437 AN: 135180 AF XY: 0.243

Gnomad AFR exome AF: 0.491

Gnomad AMR exome AF: 0.415

Gnomad ASJ exome AF: 0.239

Gnomad EAS exome AF: 0.162

Gnomad FIN exome AF: 0.169

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.259

GnomAD4 exome AF: 0.188 AC: 202427 AN: 1077080 Hom.: 5091 Cov.: 29 AF XY: 0.187 AC XY: 99713 AN XY: 534254

African (AFR) AF: 0.456 AC: 11774 AN: 25834

American (AMR) AF: 0.357 AC: 9290 AN: 26034

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 3113 AN: 17098

East Asian (EAS) AF: 0.127 AC: 3540 AN: 27954

South Asian (SAS) AF: 0.183 AC: 10725 AN: 58514

European-Finnish (FIN) AF: 0.139 AC: 5169 AN: 37258

Middle Eastern (MID) AF: 0.174 AC: 766 AN: 4408

European-Non Finnish (NFE) AF: 0.178 AC: 148764 AN: 835676

Other (OTH) AF: 0.210 AC: 9286 AN: 44304

GnomAD4 genome AF: 0.263 AC: 38944 AN: 147910 Hom.: 7362 Cov.: 23 AF XY: 0.260 AC XY: 18780 AN XY: 72098

African (AFR) AF: 0.528 AC: 21467 AN: 40690

American (AMR) AF: 0.313 AC: 4663 AN: 14906

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 482 AN: 3418

East Asian (EAS) AF: 0.0990 AC: 503 AN: 5080

South Asian (SAS) AF: 0.131 AC: 611 AN: 4656

European-Finnish (FIN) AF: 0.114 AC: 1073 AN: 9404

Middle Eastern (MID) AF: 0.150 AC: 43 AN: 286

European-Non Finnish (NFE) AF: 0.143 AC: 9502 AN: 66542

Other (OTH) AF: 0.242 AC: 491 AN: 2028

Alfa AF: 0.0682 Hom.: 60

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.42
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: rs397887772; hg19: chr6-121412191;