chrX-70284024-C-T

Variant names:

• chrX-70284024-C-T
• NM_001363807.1:c.530C>T

Variant summary

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

The NM_001363807.1(RAB41):​c.530C>T​(p.Thr177Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: RAB41 NM_001363807.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33
• Publications: 0 publications found

Genes affected

RAB41 (HGNC:18293): (RAB41, member RAS oncogene family) This gene encodes a small GTP-binding protein that belongs to the largest family within the Ras superfamily. These proteins function as regulators of membrane trafficking. They cycle between inactive GDP-bound and activated GTP-bound states, which is controlled by GTP hydrolysis-activating proteins (GAPs). This family member can be activated by the GAP protein RN-Tre, and it is localized to the Golgi complex. [provided by RefSeq, May 2010]

PDZD11 (HGNC:28034): (PDZ domain containing 11) Enables protein C-terminus binding activity. Involved in pore complex assembly. Located in basolateral plasma membrane and cytosol. Part of pore complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363807.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB41	NM_001363807.1	MANE Select	c.530C>T	p.Thr177Ile	missense	Exon 6 of 8	NP_001350736.1	Q5JT25-1
	RAB41	NM_001032726.3		c.527C>T	p.Thr176Ile	missense	Exon 6 of 8	NP_001027898.2	Q5JT25-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB41	ENST00000374473.6	TSL:5 MANE Select	c.530C>T	p.Thr177Ile	missense	Exon 6 of 8	ENSP00000363597.2	Q5JT25-1
	RAB41	ENST00000276066.4	TSL:1	c.527C>T	p.Thr176Ile	missense	Exon 6 of 8	ENSP00000276066.4	Q5JT25-2
	PDZD11	ENST00000695560.1		n.*97-1749G>A		intron	N/A	ENSP00000512017.1	Q5EBL8-1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Uncertain	-0.076	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		2.3
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.030	D
Polyphen		0.99	D
Vest4		0.36
MutPred		0.56		Gain of catalytic residue at T177 (P = 0.0157)
MVP		0.95
MPC		0.51
ClinPred		0.92	D
GERP RS		1.9
Varity_R		0.090
gMVP		0.75
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

hg19: chrX-69503874;