X-70284614-G-C

Variant names:

• chrX-70284614-G-C
• rs752092150
• NM_001363807.1:c.640G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001363807.1(RAB41):​c.640G>C​(p.Glu214Gln) 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. 16/21 in silico tools predict a benign outcome for this variant. 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: -0.265
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050843984).

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.640G>C	p.Glu214Gln	missense	Exon 8 of 8	NP_001350736.1	Q5JT25-1
	RAB41	NM_001032726.3		c.637G>C	p.Glu213Gln	missense	Exon 8 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.640G>C	p.Glu214Gln	missense	Exon 8 of 8	ENSP00000363597.2	Q5JT25-1
	RAB41	ENST00000276066.4	TSL:1	c.637G>C	p.Glu213Gln	missense	Exon 8 of 8	ENSP00000276066.4	Q5JT25-2
	PDZD11	ENST00000695561.1		n.3312C>G		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

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	Benign	0.085
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.031
DANN	Benign	0.64
DEOGEN2	Benign	0.021	T
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.41	N
PhyloP100		-0.27
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.051
Sift	Benign	0.69	T
Sift4G	Benign	0.83	T
Polyphen		0.047	B
Vest4		0.063
MutPred		0.14		Loss of glycosylation at S216 (P = 0.1298)
MVP		0.44
MPC		0.15
ClinPred		0.078	T
GERP RS		-4.8
Varity_R		0.058
gMVP		0.59
Mutation Taster		=100/0	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

dbSNP: rs752092150; hg19: chrX-69504464;