6-121091045-T-TAA

Position:

• chr6-121091045-T-TAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

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

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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.
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00122 (1411/1152062) while in subpopulation AFR AF= 0.0164 (417/25494). AF 95% confidence interval is 0.0151. There are 1 homozygotes in gnomad4_exome. There are 640 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D32	NM_152730.6	c.3466-6_3466-5dupTT		splice_region_variant, intron_variant		ENST00000398212.7	NP_689943.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D32	ENST00000398212.7	c.3466-6_3466-5dupTT		splice_region_variant, intron_variant		5	NM_152730.6	ENSP00000381270.2
TBC1D32	ENST00000275159.11	c.3589-6_3589-5dupTT		splice_region_variant, intron_variant		5		ENSP00000275159.6
TBC1D32	ENST00000464622.5	n.*4106-6_*4106-5dupTT		splice_region_variant, intron_variant		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

GnomAD3 exomes AF: 0.00217 AC: 293 AN: 135180 Hom.: 0 AF XY: 0.00169 AC XY: 123 AN XY: 72882

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 SAS exome AF: 0.00107

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

Gnomad4 AFR exome AF: 0.0164

Gnomad4 AMR exome AF: 0.00316

Gnomad4 ASJ exome AF: 0.000865

Gnomad4 EAS exome AF: 0.000588

Gnomad4 SAS exome AF: 0.00111

Gnomad4 FIN exome AF: 0.000451

Gnomad4 NFE exome AF: 0.000786

Gnomad4 OTH exome AF: 0.00161

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

Gnomad4 AFR AF: 0.00555

Gnomad4 AMR AF: 0.000268

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000150

Gnomad4 OTH AF: 0.00197

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs397887772; hg19: chr6-121412191;