rs534611598

Variant names:

• chr16-2475243-C-T
• rs534611598
• NM_001199107.2:c.-116+73C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001199107.2(TBC1D24):​c.-116+73C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 147,298 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (124 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBC1D24 NM_001199107.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.00

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-2475243-C-T is Benign according to our data. Variant chr16-2475243-C-T is described in ClinVar as [Benign]. Clinvar id is 1183617.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D24	NM_001199107.2	c.-116+73C>T		intron_variant	Intron 1 of 7	ENST00000646147.1	NP_001186036.1
TBC1D24	NM_020705.3	c.-116+73C>T		intron_variant	Intron 1 of 6		NP_065756.1
TBC1D24	XM_017023493.2	c.-116+73C>T		intron_variant	Intron 1 of 8		XP_016878982.1
TBC1D24	XM_017023495.2	c.-116+73C>T		intron_variant	Intron 1 of 7		XP_016878984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D24	ENST00000646147.1	c.-116+73C>T		intron_variant	Intron 1 of 7		NM_001199107.2	ENSP00000494678.1
TBC1D24	ENST00000567020.6	c.-116+73C>T		intron_variant	Intron 1 of 6	1		ENSP00000454408.1
TBC1D24	ENST00000569874.2	n.-116+73C>T		intron_variant	Intron 1 of 7	5		ENSP00000455005.2
TBC1D24	ENST00000630263.2	n.-142+73C>T		intron_variant	Intron 1 of 7	5		ENSP00000486835.1

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 3296 AN: 147190 Hom.: 125 Cov.: 33

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00591

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000419

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.000528

Gnomad OTH AF: 0.0188

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 60 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 34

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0225 AC: 3309 AN: 147298 Hom.: 124 Cov.: 33 AF XY: 0.0219 AC XY: 1569 AN XY: 71796

Gnomad4 AFR AF: 0.0748

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.00591

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000419

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000528

Gnomad4 OTH AF: 0.0186

Alfa AF: 0.0168 Hom.: 4

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 24, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.1
DANN	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Other links and lift over

dbSNP: rs534611598; hg19: chr16-2525244;