X-70282562-A-G

Position:

• chrX-70282562-A-G

Variant summary

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

The NM_001363807.1(RAB41):​c.154A>G​(p.Met52Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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: 23)
• Consequence: RAB41 NM_001363807.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01

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

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=0.3638965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB41	NM_001363807.1	c.154A>G	p.Met52Val	missense_variant	2/8	ENST00000374473.6	NP_001350736.1
RAB41	NM_001032726.3	c.151A>G	p.Met51Val	missense_variant	2/8		NP_001027898.2
RAB41	XM_011530948.4	c.154A>G	p.Met52Val	missense_variant	2/7		XP_011529250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB41	ENST00000374473.6	c.154A>G	p.Met52Val	missense_variant	2/8	5	NM_001363807.1	ENSP00000363597.2
RAB41	ENST00000276066.4	c.151A>G	p.Met51Val	missense_variant	2/8	1		ENSP00000276066.4
RAB41	ENST00000509895.5	c.1A>G	p.Met1?	start_lost	1/3	4		ENSP00000421643.1
PDZD11	ENST00000695560.1	n.*97-287T>C		intron_variant				ENSP00000512017.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 11, 2024

The c.151A>G (p.M51V) alteration is located in exon 2 (coding exon 2) of the RAB41 gene. This alteration results from a A to G substitution at nucleotide position 151, causing the methionine (M) at amino acid position 51 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Benign	0.45
DEOGEN2	Uncertain	0.54	.;D;.
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-0.36	.;N;.
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.021	D;T;D
Sift4G	Uncertain	0.025	D;T;T
Polyphen		0.53, 0.82	.;P;P
Vest4		0.26, 0.31
MutPred		0.51		.;Gain of helix (P = 0.1736);.;
MVP		0.70
MPC		0.17
ClinPred		0.73	D
GERP RS		0.30
Varity_R		0.41
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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-69502412;