Variant 3-100283758-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000394144.9(TBC1D23):c.423A>G(p.Pro141Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00576 in 1,613,564 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0059 ( 34 hom. )

Consequence

TBC1D23
ENST00000394144.9 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.206

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:

TBC1D23 (HGNC:):

TBC1D23 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 3-100283758-A-G is Benign according to our data. Variant chr3-100283758-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1336161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.206 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00467 (712/152362) while in subpopulation NFE AF= 0.00635 (432/68030). AF 95% confidence interval is 0.00586. There are 2 homozygotes in gnomad4. There are 304 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D23	NM_001199198.3 linkuse as main transcript	c.423A>G	p.Pro141Pro	synonymous_variant	4/19	ENST00000394144.9	NP_001186127.1	Q9NUY8-1
TBC1D23	NM_018309.5 linkuse as main transcript	c.423A>G	p.Pro141Pro	synonymous_variant	4/18		NP_060779.2	Q9NUY8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D23	ENST00000394144.9 linkuse as main transcript	c.423A>G	p.Pro141Pro	synonymous_variant	4/19	1	NM_001199198.3	ENSP00000377700.4		Q9NUY8-1

Frequencies

GnomAD3 genomes

AF:

0.00467

AC:

711

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.0317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00635

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00517

AC:

1300

AN:

251218

Hom.:

AF XY:

0.00558

AC XY:

757

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00252

Gnomad ASJ exome

AF:

0.0257

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00706

Gnomad FIN exome

AF:

0.00194

Gnomad NFE exome

AF:

0.00561

Gnomad OTH exome

AF:

0.00604

GnomAD4 exome

AF:

0.00587

AC:

8580

AN:

1461202

Hom.:

Cov.:

AF XY:

0.00589

AC XY:

4282

AN XY:

726952

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00338

Gnomad4 ASJ exome

AF:

0.0276

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00663

Gnomad4 FIN exome

AF:

0.00223

Gnomad4 NFE exome

AF:

0.00590

Gnomad4 OTH exome

AF:

0.00653

GnomAD4 genome

AF:

0.00467

AC:

712

AN:

152362

Hom.:

Cov.:

AF XY:

0.00408

AC XY:

304

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.0317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00621

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00635

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00668

Hom.:

Bravo

AF:

0.00491

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	TBC1D23: BP4, BP7, BS2 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

8.2

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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