Variant X-70283304-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001363807.1(RAB41):c.274C>T(p.Arg92Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,209,817 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 18 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.000052 ( 0 hom. 14 hem. )

Consequence

RAB41
NM_001363807.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.894

Variant links:

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]

RAB41 links:

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]

PDZD11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB41	NM_001363807.1 linkuse as main transcript	c.274C>T	p.Arg92Cys	missense_variant	4/8	ENST00000374473.6	NP_001350736.1
RAB41	NM_001032726.3 linkuse as main transcript	c.271C>T	p.Arg91Cys	missense_variant	4/8		NP_001027898.2	Q5JT25-2
RAB41	XM_011530948.4 linkuse as main transcript	c.274C>T	p.Arg92Cys	missense_variant	4/7		XP_011529250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RAB41	ENST00000374473.6 linkuse as main transcript	c.274C>T	p.Arg92Cys	missense_variant	4/8	5	NM_001363807.1	ENSP00000363597.2	Q5JT25-1
RAB41	ENST00000276066.4 linkuse as main transcript	c.271C>T	p.Arg91Cys	missense_variant	4/8	1		ENSP00000276066.4	Q5JT25-2
PDZD11	ENST00000695560.1 linkuse as main transcript	n.*97-1029G>A		intron_variant				ENSP00000512017.1	Q5EBL8-1
RAB41	ENST00000509895.5 linkuse as main transcript	c.*17C>T		downstream_gene_variant		4		ENSP00000421643.1	D6REW8

Frequencies

GnomAD3 genomes

AF:

0.0000978

AC:

AN:

112427

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

34585

show subpopulations

Gnomad AFR

AF:

0.000226

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000750

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000327

AC:

AN:

183274

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

67716

show subpopulations

Gnomad AFR exome

AF:

0.000304

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000519

AC:

AN:

1097337

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

362717

show subpopulations

Gnomad4 AFR exome

AF:

0.000265

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000511

Gnomad4 OTH exome

AF:

0.000130

GnomAD4 genome

AF:

0.000107

AC:

AN:

112480

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34648

show subpopulations

Gnomad4 AFR

AF:

0.000258

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000750

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000106

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.271C>T (p.R91C) alteration is located in exon 4 (coding exon 4) of the RAB41 gene. This alteration results from a C to T substitution at nucleotide position 271, causing the arginine (R) at amino acid position 91 to be replaced by a cysteine (C). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.70

D;.

FATHMM_MKL

Benign

0.29

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.73

D;D

MetaSVM

Uncertain

-0.15

MutationAssessor

Pathogenic

3.6

H;.

PrimateAI

Benign

0.18

PROVEAN

Pathogenic

-7.6

D;D

REVEL

Uncertain

0.42

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.49

MVP

0.93

MPC

0.76

ClinPred

1.0

GERP RS

-4.0

Varity_R

0.80

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over