16-2495894-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001199107.2(TBC1D24):c.-115-140C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00331 in 477,630 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (2 hom.)
• Consequence: TBC1D24 NM_001199107.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.292

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=-0.92).
• BP6: Variant 16-2495894-C-A is Benign according to our data. Variant chr16-2495894-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1207448.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00632 (961/151938) while in subpopulation AFR AF= 0.0171 (708/41456). AF 95% confidence interval is 0.016. There are 7 homozygotes in gnomad4. There are 444 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D24	NM_001199107.2	c.-115-140C>A		intron_variant		ENST00000646147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D24	ENST00000646147.1	c.-115-140C>A		intron_variant			NM_001199107.2	A1

Frequencies

GnomAD3 genomes AF: 0.00629 AC: 955 AN: 151820 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00853

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0224

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.00576

GnomAD4 exome AF: 0.00191 AC: 622 AN: 325692 Hom.: 2 AF XY: 0.00181 AC XY: 310 AN XY: 171676

Gnomad4 AFR exome AF: 0.0190

Gnomad4 AMR exome AF: 0.00675

Gnomad4 ASJ exome AF: 0.00684

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000728

Gnomad4 FIN exome AF: 0.0000619

Gnomad4 NFE exome AF: 0.000973

Gnomad4 OTH exome AF: 0.00408

GnomAD4 genome AF: 0.00632 AC: 961 AN: 151938 Hom.: 7 Cov.: 33 AF XY: 0.00598 AC XY: 444 AN XY: 74266

Gnomad4 AFR AF: 0.0171

Gnomad4 AMR AF: 0.00851

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00115

Gnomad4 OTH AF: 0.00570

Alfa AF: 0.00499 Hom.: 0

Bravo AF: 0.00731

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.2
Dann	Benign	0.60

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: rs147119415; hg19: chr16-2545895;