NM_002536.4:c.1351C>T

Variant names:

• chrX-48560259-C-T
• rs1556985770
• NM_002536.4:c.1351C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002536.4(TBC1D25):​c.1351C>T​(p.Gln451*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 23)
• Consequence: TBC1D25 NM_002536.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• Publications: 0 publications found

Genes affected

TBC1D25 (HGNC:8092): (TBC1 domain family member 25) This gene encodes a protein with a TBC domain and functions as a Rab GTPase activating protein. The encoded protein is involved in the fusion of autophagosomes with endosomes and lysosomes. This gene was previously known as ornithine aminotransferase-like 1, but has no similarity to ornithine aminotransferase. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D25	NM_002536.4	c.1351C>T	p.Gln451*	stop_gained	Exon 6 of 6	ENST00000376771.9	NP_002527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D25	ENST00000376771.9	c.1351C>T	p.Gln451*	stop_gained	Exon 6 of 6	1	NM_002536.4	ENSP00000365962.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	35
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.93	D
PhyloP100		1.2
Vest4		0.058
GERP RS		5.4
Mutation Taster		=22/178	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1556985770; hg19: chrX-48418647;