16-2475243-C-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_001199107.2(TBC1D24):​c.-116+73C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 60 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign 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: 0.033 (1 hom.)
• Consequence: TBC1D24 NM_001199107.2 intron
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0333 (2/60) while in subpopulation SAS AF= 0.0345 (2/58). AF 95% confidence interval is 0.00613. There are 1 homozygotes in gnomad4_exome. There are 0 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D24	NM_001199107.2	c.-116+73C>G		intron_variant	Intron 1 of 7	ENST00000646147.1	NP_001186036.1
TBC1D24	NM_020705.3	c.-116+73C>G		intron_variant	Intron 1 of 6		NP_065756.1
TBC1D24	XM_017023493.2	c.-116+73C>G		intron_variant	Intron 1 of 8		XP_016878982.1
TBC1D24	XM_017023495.2	c.-116+73C>G		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>G		intron_variant	Intron 1 of 7		NM_001199107.2	ENSP00000494678.1
TBC1D24	ENST00000567020.6	c.-116+73C>G		intron_variant	Intron 1 of 6	1		ENSP00000454408.1
TBC1D24	ENST00000569874.2	n.-116+73C>G		intron_variant	Intron 1 of 7	5		ENSP00000455005.2
TBC1D24	ENST00000630263.2	n.-142+73C>G		intron_variant	Intron 1 of 7	5		ENSP00000486835.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0333 AC: 2 AN: 60 Hom.: 1 AF XY: 0.00 AC XY: 0 AN XY: 34

Gnomad4 SAS exome AF: 0.0345

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-2525244;