Variant 3-100279700-G-A 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.105G>A(p.Thr35Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,609,444 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 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

TBC1D23
NM_001199198.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.910

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 -7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 3-100279700-G-A is Benign according to our data. Variant chr3-100279700-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3387840.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.91 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000211 (308/1457240) while in subpopulation EAS AF= 0.000505 (20/39578). AF 95% confidence interval is 0.000334. There are 1 homozygotes in gnomad4_exome. There are 140 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D23	NM_001199198.3 linkuse as main transcript	c.105G>A	p.Thr35Thr	synonymous_variant	2/19	ENST00000394144.9	NP_001186127.1	Q9NUY8-1
TBC1D23	NM_018309.5 linkuse as main transcript	c.105G>A	p.Thr35Thr	synonymous_variant	2/18		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.105G>A	p.Thr35Thr	synonymous_variant	2/19	1	NM_001199198.3	ENSP00000377700.4		Q9NUY8-1

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000244

AC:

AN:

249560

Hom.:

AF XY:

0.000259

AC XY:

AN XY:

134970

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000273

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000320

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000211

AC:

308

AN:

1457240

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

140

AN XY:

724798

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000505

Gnomad4 SAS exome

AF:

0.000164

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000221

Gnomad4 OTH exome

AF:

0.000200

GnomAD4 genome

AF:

0.000177

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000229

Hom.:

Bravo

AF:

0.000234

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

TBC1D23: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.72

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