rs12373107

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001199107.2(TBC1D24):c.1440G>A(p.Ser480Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 1,601,820 control chromosomes in the GnomAD database, including 874 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 70 hom., cov: 33)

Exomes 𝑓: 0.029 ( 804 hom. )

Consequence

TBC1D24
NM_001199107.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -6.62

Publications

6 publications found

Variant links:

Genes affected

TBC1D24 (HGNC:29203): (TBC1 domain family member 24) This gene encodes a protein with a conserved domain, referred to as the TBC domain, characteristic of proteins which interact with GTPases. TBC domain proteins may serve as GTPase-activating proteins for a particular group of GTPases, the Rab (Ras-related proteins in brain) small GTPases which are involved in the regulation of membrane trafficking. Mutations in this gene are associated with familial infantile myoclonic epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2011]

TBC1D24 Gene-Disease associations (from GenCC):

DOORS syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, ClinGen, Ambry Genetics
familial infantile myoclonic epilepsy
Inheritance: AR Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, G2P
autosomal dominant nonsyndromic hearing loss 65
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
autosomal recessive nonsyndromic hearing loss 86
Inheritance: AR Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics
developmental and epileptic encephalopathy, 16
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
malignant migrating partial seizures of infancy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
focal epilepsy-intellectual disability-cerebro-cerebellar malformation
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
progressive myoclonic epilepsy with dystonia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
nonsyndromic genetic hearing loss
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

TBC1D24 links:

ENSG00000260272 (HGNC:):

ENSG00000260272 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 16-2500405-G-A is Benign according to our data. Variant chr16-2500405-G-A is described in ClinVar as Benign. ClinVar VariationId is 130536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.62 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.064 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199107.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D24	NM_001199107.2	MANE Select	c.1440G>A	p.Ser480Ser	synonymous	Exon 7 of 8	NP_001186036.1	Q9ULP9-1
	TBC1D24	NM_020705.3		c.1422G>A	p.Ser474Ser	synonymous	Exon 6 of 7	NP_065756.1	Q9ULP9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBC1D24	ENST00000646147.1	MANE Select	c.1440G>A	p.Ser480Ser	synonymous	Exon 7 of 8	ENSP00000494678.1	Q9ULP9-1
TBC1D24	ENST00000567020.7	TSL:1	c.1422G>A	p.Ser474Ser	synonymous	Exon 6 of 7	ENSP00000454408.1	Q9ULP9-2
ENSG00000260272	ENST00000564543.1	TSL:2	c.965+3292G>A		intron	N/A	ENSP00000455547.1	H3BQ06

Frequencies

GnomAD3 genomes

AF:

0.0232

AC:

3532

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00700

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0674

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0263

Gnomad FIN

AF:

0.0154

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0263

Gnomad OTH

AF:

0.0220

GnomAD2 exomes

AF:

0.0320

AC:

7039

AN:

219852

AF XY:

0.0305

show subpopulations

Gnomad AFR exome

AF:

0.00777

Gnomad AMR exome

AF:

0.0928

Gnomad ASJ exome

AF:

0.0196

Gnomad EAS exome

AF:

0.000179

Gnomad FIN exome

AF:

0.0136

Gnomad NFE exome

AF:

0.0262

Gnomad OTH exome

AF:

0.0291

GnomAD4 exome

AF:

0.0289

AC:

41889

AN:

1449554

Hom.:

804

Cov.:

AF XY:

0.0289

AC XY:

20800

AN XY:

720002

show subpopulations

African (AFR)

AF:

0.00545

AC:

181

AN:

33192

American (AMR)

AF:

0.0865

AC:

3772

AN:

43594

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

484

AN:

25840

East Asian (EAS)

AF:

0.000179

AC:

AN:

39080

South Asian (SAS)

AF:

0.0301

AC:

2529

AN:

84018

European-Finnish (FIN)

AF:

0.0157

AC:

806

AN:

51294

Middle Eastern (MID)

AF:

0.00977

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.0294

AC:

32596

AN:

1106956

Other (OTH)

AF:

0.0244

AC:

1458

AN:

59846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

2502

5003

7505

10006

12508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1282

2564

3846

5128

6410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0232

AC:

3532

AN:

152266

Hom.:

Cov.:

AF XY:

0.0231

AC XY:

1721

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.00698

AC:

290

AN:

41566

American (AMR)

AF:

0.0674

AC:

1030

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0176

AC:

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5188

South Asian (SAS)

AF:

0.0263

AC:

127

AN:

4822

European-Finnish (FIN)

AF:

0.0154

AC:

164

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0263

AC:

1789

AN:

68000

Other (OTH)

AF:

0.0218

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

162

324

486

648

810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0229

Hom.:

Bravo

AF:

0.0268

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

not provided (2)

Developmental and epileptic encephalopathy, 1;C3892048:Autosomal dominant nonsyndromic hearing loss 65;CN236805:Caused by mutation in the TBC1 domain family, member 24 (1)

Familial infantile myoclonic epilepsy (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.050

(source)

DANN

Benign

0.88

PhyloP100

-6.6

Mutation Taster

=100/0

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over