16-30358146-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_015527.4(TBC1D10B):c.2225G>A(p.Arg742Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000071 in 1,549,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R742L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

TBC1D10B
NM_015527.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.723

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026023299).

BP6

Variant 16-30358146-C-T is Benign according to our data. Variant chr16-30358146-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2344939.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D10B	NM_015527.4 link	c.2225G>A	p.Arg742Gln	missense_variant	Exon 9 of 9	ENST00000409939.8	NP_056342.3	Q4KMP7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D10B	ENST00000409939.8 link	c.2225G>A	p.Arg742Gln	missense_variant	Exon 9 of 9	1	NM_015527.4	ENSP00000386538.3		Q4KMP7-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151776

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000506

AC:

AN:

157954

AF XY:

0.0000363

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000234

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000652

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000751

AC:

105

AN:

1397580

Hom.:

Cov.:

AF XY:

0.0000783

AC XY:

AN XY:

689238

show subpopulations

African (AFR)

AF:

0.0000634

AC:

AN:

31560

American (AMR)

AF:

0.00

AC:

AN:

35652

Ashkenazi Jewish (ASJ)

AF:

0.0000795

AC:

AN:

25172

East Asian (EAS)

AF:

0.00

AC:

AN:

35630

South Asian (SAS)

AF:

0.0000127

AC:

AN:

79006

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49464

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.0000873

AC:

AN:

1077364

Other (OTH)

AF:

0.000103

AC:

AN:

58044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000329

AC:

AN:

151776

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74154

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41280

American (AMR)

AF:

0.00

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67900

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jul 06, 2021

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.9

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0050

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.031

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.079

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.1

PhyloP100

-0.72

PrimateAI

Benign

0.26

PROVEAN

Benign

0.56

REVEL

Benign

0.15

Sift

Benign

0.86

Sift4G

Benign

0.62

Polyphen

0.0

Vest4

0.066

MutPred

0.17

Loss of MoRF binding (P = 0.015);

MVP

0.23

MPC

0.14

ClinPred

0.015

GERP RS

2.2

Varity_R

0.029

gMVP

0.054

Mutation Taster

=97/3

polymorphism

(source)

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

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16-30358146-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over