Variant 16-30358146-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015527.4(TBC1D10B):c.2225G>T(p.Arg742Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00236 in 1,549,474 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 4 hom. )

Consequence

TBC1D10B
NM_015527.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.723

Variant links:

Genes affected

TBC1D10B (HGNC:24510): (TBC1 domain family member 10B) Small G proteins of the RAB family (see MIM 179508) function in intracellular vesicle trafficking by switching from the GTP-bound state to the GDP-bound state with the assistance of guanine nucleotide exchange factors (GEFs; see MIM 609700) and GTPase-activating proteins (GAPs). TBC1D10B functions as a GAP for several proteins of the Rab family (Ishibashi et al., 2009 [PubMed 19077034]).[supplied by OMIM, Nov 2010]

TBC1D10B links:

CD2BP2-DT (HGNC:53029): (CD2BP2 divergent transcript)

CD2BP2-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004202485).

BS2

High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D10B	NM_015527.4 link	c.2225G>T	p.Arg742Leu	missense_variant	9/9	ENST00000409939.8	NP_056342.3	Q4KMP7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D10B	ENST00000409939.8 link	c.2225G>T	p.Arg742Leu	missense_variant	9/9	1	NM_015527.4	ENSP00000386538.3		Q4KMP7-1

Frequencies

GnomAD3 genomes

AF:

0.00139

AC:

211

AN:

151776

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000678

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00228

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00130

AC:

205

AN:

157954

Hom.:

AF XY:

0.00120

AC XY:

AN XY:

82752

show subpopulations

Gnomad AFR exome

AF:

0.000777

Gnomad AMR exome

AF:

0.000686

Gnomad ASJ exome

AF:

0.000234

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000769

Gnomad NFE exome

AF:

0.00262

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00246

AC:

3445

AN:

1397580

Hom.:

Cov.:

AF XY:

0.00236

AC XY:

1628

AN XY:

689238

show subpopulations

Gnomad4 AFR exome

AF:

0.000317

Gnomad4 AMR exome

AF:

0.000813

Gnomad4 ASJ exome

AF:

0.000199

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.000748

Gnomad4 NFE exome

AF:

0.00302

Gnomad4 OTH exome

AF:

0.00181

GnomAD4 genome

AF:

0.00139

AC:

211

AN:

151894

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.000676

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.00228

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00200

Hom.:

Bravo

AF:

0.00138

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.00123

AC:

ESP6500EA

AF:

0.00262

AC:

ExAC

AF:

0.000504

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 29, 2023

The c.2225G>T (p.R742L) alteration is located in exon 9 (coding exon 9) of the TBC1D10B gene. This alteration results from a G to T substitution at nucleotide position 2225, causing the arginine (R) at amino acid position 742 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.32

CADD

Benign

9.9

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0046

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.052

LIST_S2

Uncertain

0.88

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.0042

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.62

REVEL

Benign

0.091

Sift

Uncertain

0.0060

Sift4G

Benign

0.21

Polyphen

0.023

Vest4

0.24

MVP

0.13

MPC

0.15

ClinPred

0.017

GERP RS

2.2

Varity_R

0.11

gMVP

0.081

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

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