6-121080850-T-G

Position:

• chr6-121080850-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_152730.6(TBC1D32):​c.3695A>C​(p.Glu1232Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0163 in 1,613,910 control chromosomes in the GnomAD database, including 258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (14 hom., cov: 31)
  • Exomes 𝑓: 0.017 (244 hom.)
• Consequence: TBC1D32 NM_152730.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.16

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0055611134).
• BP6: Variant 6-121080850-T-G is Benign according to our data. Variant chr6-121080850-T-G is described in ClinVar as [Benign]. Clinvar id is 1541792.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0144 (2195/152288) while in subpopulation SAS AF= 0.0191 (92/4828). AF 95% confidence interval is 0.0159. There are 14 homozygotes in gnomad4. There are 1037 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D32	NM_152730.6	c.3695A>C	p.Glu1232Ala	missense_variant	32/32	ENST00000398212.7	NP_689943.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D32	ENST00000398212.7	c.3695A>C	p.Glu1232Ala	missense_variant	32/32	5	NM_152730.6	ENSP00000381270.2
TBC1D32	ENST00000275159.11	c.3818A>C	p.Glu1273Ala	missense_variant	33/33	5		ENSP00000275159.6
TBC1D32	ENST00000464622.5	n.*4335A>C		non_coding_transcript_exon_variant	36/36	2		ENSP00000428839.1
TBC1D32	ENST00000464622.5	n.*4335A>C		3_prime_UTR_variant	36/36	2		ENSP00000428839.1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2196 AN: 152170 Hom.: 13 Cov.: 31

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.0172

GnomAD3 exomes AF: 0.0146 AC: 3634 AN: 248718 Hom.: 35 AF XY: 0.0155 AC XY: 2098 AN XY: 134992

Gnomad AFR exome AF: 0.0135

Gnomad AMR exome AF: 0.00949

Gnomad ASJ exome AF: 0.00757

Gnomad EAS exome AF: 0.0000558

Gnomad SAS exome AF: 0.0227

Gnomad FIN exome AF: 0.0139

Gnomad NFE exome AF: 0.0172

Gnomad OTH exome AF: 0.0153

GnomAD4 exome AF: 0.0165 AC: 24149 AN: 1461622 Hom.: 244 Cov.: 30 AF XY: 0.0169 AC XY: 12265 AN XY: 727104

Gnomad4 AFR exome AF: 0.0156

Gnomad4 AMR exome AF: 0.0105

Gnomad4 ASJ exome AF: 0.00773

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0223

Gnomad4 FIN exome AF: 0.0136

Gnomad4 NFE exome AF: 0.0173

Gnomad4 OTH exome AF: 0.0155

GnomAD4 genome AF: 0.0144 AC: 2195 AN: 152288 Hom.: 14 Cov.: 31 AF XY: 0.0139 AC XY: 1037 AN XY: 74462

Gnomad4 AFR AF: 0.0142

Gnomad4 AMR AF: 0.0119

Gnomad4 ASJ AF: 0.00806

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0191

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.0167

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0168 Hom.: 43

Bravo AF: 0.0140

TwinsUK AF: 0.0170 AC: 63

ALSPAC AF: 0.0161 AC: 62

ESP6500AA AF: 0.0117 AC: 44

ESP6500EA AF: 0.0156 AC: 129

ExAC AF: 0.0146 AC: 1760

Asia WGS AF: 0.0110 AC: 37 AN: 3478

EpiCase AF: 0.0201

EpiControl AF: 0.0168

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

Dec 21, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	.;T
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.86	D;D
MetaRNN	Benign	0.0056	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	.;M
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.047
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.030	D;D
Polyphen		0.095	.;B
Vest4		0.19
MPC		0.17
ClinPred		0.041	T
GERP RS		5.5
Varity_R		0.19
gMVP		0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs56300302; hg19: chr6-121401996;