Variant 16-2500807-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001199107.2(TBC1D24):c.1529G>T(p.Gly510Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TBC1D24
NM_001199107.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.60

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 links:

ENSG00000260272 (HGNC:):

ENSG00000260272 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.961

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D24	NM_001199107.2 linkuse as main transcript	c.1529G>T	p.Gly510Val	missense_variant	8/8	ENST00000646147.1	NP_001186036.1	Q9ULP9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D24	ENST00000646147.1 linkuse as main transcript	c.1529G>T	p.Gly510Val	missense_variant	8/8		NM_001199107.2	ENSP00000494678.1		Q9ULP9-1
ENSG00000260272	ENST00000564543.1 linkuse as main transcript	c.965+3694G>T		intron_variant		2		ENSP00000455547.1		H3BQ06

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000421

AC:

AN:

237488

Hom.:

AF XY:

0.00

AC XY:

AN XY:

130160

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000905

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1451768

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722646

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000825

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

.;T;T;.

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

.;.;D;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.96

D;D;D;D

MetaSVM

Uncertain

0.042

MutationAssessor

Pathogenic

4.0

.;H;H;.

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-7.3

D;.;D;.

REVEL

Uncertain

0.60

Sift

Uncertain

0.0010

D;.;D;.

Sift4G

Uncertain

0.0040

D;.;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.87

MutPred

0.82

.;Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;

MVP

0.90

MPC

1.2

ClinPred

1.0

GERP RS

5.8

Varity_R

0.96

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.39

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.39

Position offset: 3

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over