Variant chr3-100261031-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001199198.3(TBC1D23):c.13G>A(p.Glu5Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TBC1D23
NM_001199198.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.51

Variant links:

Genes affected

TBC1D23 (HGNC:25622): (TBC1 domain family member 23) Involved in brain development; retrograde transport, endosome to Golgi; and vesicle tethering to Golgi. Located in cytoplasmic vesicle and trans-Golgi network. Colocalizes with WASH complex. Implicated in pontocerebellar hypoplasia. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13761213).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D23	NM_001199198.3 linkuse as main transcript	c.13G>A	p.Glu5Lys	missense_variant	1/19	ENST00000394144.9
TBC1D23	NM_018309.5 linkuse as main transcript	c.13G>A	p.Glu5Lys	missense_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D23	ENST00000394144.9 linkuse as main transcript	c.13G>A	p.Glu5Lys	missense_variant	1/19	1	NM_001199198.3	P3	Q9NUY8-1
TBC1D23	ENST00000344949.9 linkuse as main transcript	c.13G>A	p.Glu5Lys	missense_variant	1/18	1		A1	Q9NUY8-2
TBC1D23	ENST00000485687.5 linkuse as main transcript	c.13G>A	p.Glu5Lys	missense_variant	1/5	3
TBC1D23	ENST00000486274.5 linkuse as main transcript			upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152278

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461704

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

0.0014

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

.;.;T

Eigen

Benign

-0.15

Eigen_PC

Benign

0.036

FATHMM_MKL

Benign

0.56

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.0074

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

.;N;N

MutationTaster

Benign

0.77

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.71

N;N;N

REVEL

Benign

0.027

Sift

Uncertain

0.010

D;D;D

Sift4G

Uncertain

0.044

D;T;T

Polyphen

0.029, 0.017

.;B;B

Vest4

0.48, 0.48

MutPred

0.22

Gain of ubiquitination at E5 (P = 0.0016);Gain of ubiquitination at E5 (P = 0.0016);Gain of ubiquitination at E5 (P = 0.0016);

MVP

0.45

MPC

0.29

ClinPred

0.83

GERP RS

4.9

Varity_R

0.29

gMVP

0.26

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