Variant 6-121106137-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_152730.6(TBC1D32):c.3351A>G(p.Glu1117=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 1,570,316 control chromosomes in the GnomAD database, including 606 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 44 hom., cov: 32)

Exomes 𝑓: 0.025 ( 562 hom. )

Consequence

TBC1D32
NM_152730.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.134

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 6-121106137-T-C is Benign according to our data. Variant chr6-121106137-T-C is described in ClinVar as [Benign]. Clinvar id is 1600966.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.134 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0196 (2986/152038) while in subpopulation NFE AF= 0.0289 (1964/67948). AF 95% confidence interval is 0.0278. There are 44 homozygotes in gnomad4. There are 1453 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D32	NM_152730.6 linkuse as main transcript	c.3351A>G	p.Glu1117=	synonymous_variant	30/32	ENST00000398212.7	NP_689943.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D32	ENST00000398212.7 linkuse as main transcript	c.3351A>G	p.Glu1117=	synonymous_variant	30/32	5	NM_152730.6	ENSP00000381270		Q96NH3-1

Frequencies

GnomAD3 genomes

AF:

0.0197

AC:

2988

AN:

151920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00515

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0263

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.0272

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0289

Gnomad OTH

AF:

0.0249

GnomAD3 exomes

AF:

0.0198

AC:

4887

AN:

246392

Hom.:

AF XY:

0.0195

AC XY:

2616

AN XY:

133826

show subpopulations

Gnomad AFR exome

AF:

0.00493

Gnomad AMR exome

AF:

0.0193

Gnomad ASJ exome

AF:

0.0156

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00333

Gnomad FIN exome

AF:

0.0288

Gnomad NFE exome

AF:

0.0281

Gnomad OTH exome

AF:

0.0231

GnomAD4 exome

AF:

0.0251

AC:

35616

AN:

1418278

Hom.:

562

Cov.:

AF XY:

0.0246

AC XY:

17344

AN XY:

704458

show subpopulations

Gnomad4 AFR exome

AF:

0.00431

Gnomad4 AMR exome

AF:

0.0195

Gnomad4 ASJ exome

AF:

0.0155

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00391

Gnomad4 FIN exome

AF:

0.0303

Gnomad4 NFE exome

AF:

0.0286

Gnomad4 OTH exome

AF:

0.0224

GnomAD4 genome

AF:

0.0196

AC:

2986

AN:

152038

Hom.:

Cov.:

AF XY:

0.0195

AC XY:

1453

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00513

Gnomad4 AMR

AF:

0.0263

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00374

Gnomad4 FIN

AF:

0.0272

Gnomad4 NFE

AF:

0.0289

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0240

Hom.:

Bravo

AF:

0.0194

Asia WGS

AF:

0.00202

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.22

DANN

Benign

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over