Variant rs10101626 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 3P and 8B. PVS1_ModeratePP3BA1

The NM_145647.4(TBC1D31):c.2835+1G>T variant causes a splice donor change. The variant allele was found at a frequency of 0.189 in 1,534,894 control chromosomes in the GnomAD database, including 28,132 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3251 hom., cov: 31)

Exomes 𝑓: 0.19 ( 24881 hom. )

Consequence

TBC1D31
NM_145647.4 splice_donor

Scores

Splicing: ADA: 1.000

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.60

Variant links:

Genes affected

TBC1D31 (HGNC:30888): (TBC1 domain family member 31) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D31 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.060606062 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

PP3

Multiple lines of computational evidence support a deleterious effect 5: Cadd, dbscSNV1_ADA, dbscSNV1_RF, max_spliceai, Eigen [when BayesDel_addAF, MutationTaster was below the threshold]

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D31	NM_145647.4 linkuse as main transcript	c.2835+1G>T		splice_donor_variant		ENST00000287380.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D31	ENST00000287380.6 linkuse as main transcript	c.2835+1G>T		splice_donor_variant		1	NM_145647.4	P1	Q96DN5-1

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

30898

AN:

150920

Hom.:

3244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.114

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.204

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.193

GnomAD3 exomes

AF:

0.193

AC:

36583

AN:

189302

Hom.:

3541

AF XY:

0.194

AC XY:

20196

AN XY:

103880

show subpopulations

Gnomad AFR exome

AF:

0.248

Gnomad AMR exome

AF:

0.175

Gnomad ASJ exome

AF:

0.208

Gnomad EAS exome

AF:

0.201

Gnomad SAS exome

AF:

0.225

Gnomad FIN exome

AF:

0.161

Gnomad NFE exome

AF:

0.187

Gnomad OTH exome

AF:

0.191

GnomAD4 exome

AF:

0.188

AC:

259618

AN:

1383864

Hom.:

24881

Cov.:

AF XY:

0.188

AC XY:

129011

AN XY:

685516

show subpopulations

Gnomad4 AFR exome

AF:

0.247

Gnomad4 AMR exome

AF:

0.167

Gnomad4 ASJ exome

AF:

0.207

Gnomad4 EAS exome

AF:

0.206

Gnomad4 SAS exome

AF:

0.218

Gnomad4 FIN exome

AF:

0.169

Gnomad4 NFE exome

AF:

0.184

Gnomad4 OTH exome

AF:

0.194

GnomAD4 genome

AF:

0.205

AC:

30922

AN:

151030

Hom.:

3251

Cov.:

AF XY:

0.204

AC XY:

15025

AN XY:

73778

show subpopulations

Gnomad4 AFR

AF:

0.248

Gnomad4 AMR

AF:

0.185

Gnomad4 ASJ

AF:

0.205

Gnomad4 EAS

AF:

0.205

Gnomad4 SAS

AF:

0.221

Gnomad4 FIN

AF:

0.160

Gnomad4 NFE

AF:

0.191

Gnomad4 OTH

AF:

0.190

Alfa

AF:

0.195

Hom.:

7006

Bravo

AF:

0.208

TwinsUK

AF:

0.201

AC:

746

ALSPAC

AF:

0.191

AC:

736

ExAC

AF:

0.195

AC:

23628

Asia WGS

AF:

0.217

AC:

752

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

0.97

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Uncertain

0.95

MutationTaster

Benign

1.7e-37

P;P;P;P;P;P;P

GERP RS

5.4

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.87

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.99

Position offset: -1

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over