Variant 3-100283659-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS1

The NM_001199198.3(TBC1D23):c.324A>G(p.Glu108=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000429 in 1,613,828 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00044 ( 1 hom. )

Consequence

TBC1D23
NM_001199198.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.08

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 3-100283659-A-G is Benign according to our data. Variant chr3-100283659-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2654003.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.08 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000374 (57/152314) while in subpopulation NFE AF= 0.000573 (39/68030). AF 95% confidence interval is 0.000431. There are 0 homozygotes in gnomad4. There are 21 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D23	NM_001199198.3 linkuse as main transcript	c.324A>G	p.Glu108=	synonymous_variant	4/19	ENST00000394144.9
TBC1D23	NM_018309.5 linkuse as main transcript	c.324A>G	p.Glu108=	synonymous_variant	4/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D23	ENST00000394144.9 linkuse as main transcript	c.324A>G	p.Glu108=	synonymous_variant	4/19	1	NM_001199198.3	P3	Q9NUY8-1

Frequencies

GnomAD3 genomes

AF:

0.000375

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000231

AC:

AN:

251180

Hom.:

AF XY:

0.000221

AC XY:

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000440

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000435

AC:

636

AN:

1461514

Hom.:

Cov.:

AF XY:

0.000436

AC XY:

317

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.000535

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000374

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000355

EpiCase

AF:

0.000600

EpiControl

AF:

0.000889

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

TBC1D23-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 12, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

TBC1D23: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

8.6

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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