X-48539907-G-A

Position:

• chrX-48539907-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002536.4(TBC1D25):​c.110G>A​(p.Arg37Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: TBC1D25 NM_002536.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.65

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28143722).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D25	NM_002536.4	c.110G>A	p.Arg37Gln	missense_variant	1/6	ENST00000376771.9	NP_002527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D25	ENST00000376771.9	c.110G>A	p.Arg37Gln	missense_variant	1/6	1	NM_002536.4	ENSP00000365962	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 844184 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 259606

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

TBC1D25: PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	T;.
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.15
Sift	Benign	0.089	T;D
Sift4G	Benign	0.10	T;D
Polyphen		0.0060	B;.
Vest4		0.47
MutPred		0.28		Gain of ubiquitination at K42 (P = 0.0369);Gain of ubiquitination at K42 (P = 0.0369);
MVP		0.26
MPC		0.92
ClinPred		0.90	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.20
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: chrX-48398295;