16-2500357-C-T
Variant names:
Variant summary
Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001199107.2(TBC1D24):c.1392C>T(p.Thr464Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,609,718 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00015 ( 4 hom. )
Consequence
TBC1D24
NM_001199107.2 synonymous
NM_001199107.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.13
Publications
0 publications found
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 syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, PanelApp Australia, G2P
- familial infantile myoclonic epilepsyInheritance: AR Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet
- autosomal dominant nonsyndromic hearing loss 65Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
- autosomal dominant nonsyndromic hearing lossInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- malignant migrating partial seizures of infancyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- focal epilepsy-intellectual disability-cerebro-cerebellar malformationInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- hearing loss, autosomal recessiveInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- progressive myoclonic epilepsy with dystoniaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- nonsyndromic genetic hearing lossInheritance: AD Classification: LIMITED Submitted by: ClinGen
- autosomal recessive nonsyndromic hearing loss 86Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
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=-0.77).
BP6
Variant 16-2500357-C-T is Benign according to our data. Variant chr16-2500357-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 238626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.13 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000151 (23/152316) while in subpopulation EAS AF = 0.00347 (18/5188). AF 95% confidence interval is 0.00224. There are 0 homozygotes in GnomAd4. There are 14 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
BS2
High Homozygotes in GnomAdExome4 at 4 AR,AD gene
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TBC1D24 | ENST00000646147.1 | c.1392C>T | p.Thr464Thr | synonymous_variant | Exon 7 of 8 | NM_001199107.2 | ENSP00000494678.1 | |||
ENSG00000260272 | ENST00000564543.1 | c.965+3244C>T | intron_variant | Intron 1 of 2 | 2 | ENSP00000455547.1 |
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152198Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
23
AN:
152198
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000684 AC: 16AN: 233776 AF XY: 0.0000702 show subpopulations
GnomAD2 exomes
AF:
AC:
16
AN:
233776
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000154 AC: 225AN: 1457402Hom.: 4 Cov.: 33 AF XY: 0.000148 AC XY: 107AN XY: 724716 show subpopulations
GnomAD4 exome
AF:
AC:
225
AN:
1457402
Hom.:
Cov.:
33
AF XY:
AC XY:
107
AN XY:
724716
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33392
American (AMR)
AF:
AC:
2
AN:
44516
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26018
East Asian (EAS)
AF:
AC:
192
AN:
39544
South Asian (SAS)
AF:
AC:
6
AN:
85438
European-Finnish (FIN)
AF:
AC:
0
AN:
51958
Middle Eastern (MID)
AF:
AC:
1
AN:
5742
European-Non Finnish (NFE)
AF:
AC:
23
AN:
1110658
Other (OTH)
AF:
AC:
1
AN:
60136
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.486
Heterozygous variant carriers
0
16
32
49
65
81
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
4
8
12
16
20
<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: 0.000151 AC: 23AN: 152316Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74480 show subpopulations
GnomAD4 genome
AF:
AC:
23
AN:
152316
Hom.:
Cov.:
33
AF XY:
AC XY:
14
AN XY:
74480
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41560
American (AMR)
AF:
AC:
5
AN:
15314
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
18
AN:
5188
South Asian (SAS)
AF:
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68008
Other (OTH)
AF:
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.497
Heterozygous variant carriers
0
2
3
5
6
8
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
0
2
4
6
8
10
<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:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
2
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Sep 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
TBC1D24: BP4, BP7 -
Developmental and epileptic encephalopathy, 1;C3892048:Autosomal dominant nonsyndromic hearing loss 65;CN236805:Caused by mutation in the TBC1 domain family, member 24 Benign:1
Dec 05, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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