6-121321644-T-C

Variant names:

• chr6-121321644-T-C
• rs10499110
• NM_152730.6:c.306A>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_152730.6(TBC1D32):​c.306A>G​(p.Gln102Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 1,612,726 control chromosomes in the GnomAD database, including 1,876 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.052 (400 hom., cov: 32)
  • Exomes 𝑓: 0.023 (1476 hom.)
• Consequence: TBC1D32 NM_152730.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0270
• 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 6-121321644-T-C is Benign according to our data. Variant chr6-121321644-T-C is described in ClinVar as Benign. ClinVar VariationId is 1560549.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.027 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D32	NM_152730.6	c.306A>G	p.Gln102Gln	synonymous_variant	Exon 2 of 32	ENST00000398212.7	NP_689943.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D32	ENST00000398212.7	c.306A>G	p.Gln102Gln	synonymous_variant	Exon 2 of 32	5	NM_152730.6	ENSP00000381270.2
TBC1D32	ENST00000275159.11	c.306A>G	p.Gln102Gln	synonymous_variant	Exon 2 of 33	5		ENSP00000275159.6
TBC1D32	ENST00000464622.5	n.306A>G		non_coding_transcript_exon_variant	Exon 2 of 36	2		ENSP00000428839.1
TBC1D32	ENST00000422369.1	c.306A>G	p.Gln102Gln	synonymous_variant	Exon 3 of 6	3		ENSP00000397993.1

Frequencies

GnomAD3 genomes AF: 0.0515 AC: 7839 AN: 152114 Hom.: 400 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0291

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0132

Gnomad OTH AF: 0.0483

GnomAD2 exomes AF: 0.0491 AC: 12170 AN: 247982 AF XY: 0.0404

Gnomad AFR exome AF: 0.0994

Gnomad AMR exome AF: 0.168

Gnomad ASJ exome AF: 0.00918

Gnomad EAS exome AF: 0.109

Gnomad FIN exome AF: 0.0281

Gnomad NFE exome AF: 0.0155

Gnomad OTH exome AF: 0.0359

GnomAD4 exome AF: 0.0232 AC: 33873 AN: 1460494 Hom.: 1476 Cov.: 31 AF XY: 0.0215 AC XY: 15638 AN XY: 726518

African (AFR) AF: 0.100 AC: 3343 AN: 33292

American (AMR) AF: 0.159 AC: 7078 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.0102 AC: 265 AN: 26090

East Asian (EAS) AF: 0.144 AC: 5708 AN: 39664

South Asian (SAS) AF: 0.00985 AC: 846 AN: 85928

European-Finnish (FIN) AF: 0.0290 AC: 1549 AN: 53400

Middle Eastern (MID) AF: 0.00885 AC: 51 AN: 5764

European-Non Finnish (NFE) AF: 0.0121 AC: 13419 AN: 1111502

Other (OTH) AF: 0.0267 AC: 1614 AN: 60346

GnomAD4 genome AF: 0.0516 AC: 7850 AN: 152232 Hom.: 400 Cov.: 32 AF XY: 0.0528 AC XY: 3928 AN XY: 74422

African (AFR) AF: 0.101 AC: 4187 AN: 41538

American (AMR) AF: 0.108 AC: 1645 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 38 AN: 3472

East Asian (EAS) AF: 0.117 AC: 603 AN: 5154

South Asian (SAS) AF: 0.0124 AC: 60 AN: 4828

European-Finnish (FIN) AF: 0.0291 AC: 309 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0132 AC: 901 AN: 68016

Other (OTH) AF: 0.0497 AC: 105 AN: 2114

Alfa AF: 0.0289 Hom.: 73

Bravo AF: 0.0631

Asia WGS AF: 0.0880 AC: 306 AN: 3478

EpiCase AF: 0.0114

EpiControl AF: 0.0116

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 24, 2025

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
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.1
DANN	Benign	0.38
PhyloP100		0.027
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	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: rs10499110; hg19: chr6-121642790; COSMIC: COSV51536520;