chr6-121091045-T-TAA

Variant names:

• chr6-121091045-T-TAA
• rs397887772
• NM_152730.6:c.3466-6_3466-5dupTT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_152730.6(TBC1D32):​c.3466-6_3466-5dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,300,080 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0012 (1 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 6-121091045-T-TAA is Benign according to our data. Variant chr6-121091045-T-TAA is described in ClinVar as [Benign]. Clinvar id is 2727306.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00158 AC: 233 AN: 147934 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00551

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000269

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00199

GnomAD2 exomes AF: 0.00217 AC: 293 AN: 135180 AF XY: 0.00169

Gnomad AFR exome AF: 0.0132

Gnomad AMR exome AF: 0.00365

Gnomad ASJ exome AF: 0.00103

Gnomad EAS exome AF: 0.000854

Gnomad FIN exome AF: 0.000632

Gnomad NFE exome AF: 0.000585

Gnomad OTH exome AF: 0.00103

GnomAD4 exome AF: 0.00122 AC: 1411 AN: 1152062 Hom.: 1 Cov.: 29 AF XY: 0.00112 AC XY: 640 AN XY: 571296

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0164 AC: 417 AN: 25494

American (AMR) AF: 0.00316 AC: 85 AN: 26874

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 16 AN: 18494

East Asian (EAS) AF: 0.000588 AC: 18 AN: 30626

South Asian (SAS) AF: 0.00111 AC: 70 AN: 62990

European-Finnish (FIN) AF: 0.000451 AC: 18 AN: 39948

Middle Eastern (MID) AF: 0.00150 AC: 7 AN: 4654

European-Non Finnish (NFE) AF: 0.000786 AC: 704 AN: 895650

Other (OTH) AF: 0.00161 AC: 76 AN: 47332

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00159 AC: 235 AN: 148018 Hom.: 0 Cov.: 23 AF XY: 0.00150 AC XY: 108 AN XY: 72154

African (AFR) AF: 0.00555 AC: 226 AN: 40738

American (AMR) AF: 0.000268 AC: 4 AN: 14914

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3418

East Asian (EAS) AF: 0.00 AC: 0 AN: 5082

South Asian (SAS) AF: 0.00 AC: 0 AN: 4658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66582

Other (OTH) AF: 0.00197 AC: 4 AN: 2028

Alfa AF: 0.000921 Hom.: 60

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 12, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs397887772; hg19: chr6-121412191;