rs141218284

Variant names:

• chrX-70283553-C-T
• rs141218284
• NM_001363807.1:c.384C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001363807.1(RAB41):​c.384C>T​(p.His128His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,095,536 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000055 (0 hom. 2 hem.)
• Consequence: RAB41 NM_001363807.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.622
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant X-70283553-C-T is Benign according to our data. Variant chrX-70283553-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2660812.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.622 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

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.384C>T	p.His128His	synonymous	Exon 5 of 8	NP_001350736.1	Q5JT25-1
	RAB41	NM_001032726.3		c.381C>T	p.His127His	synonymous	Exon 5 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.384C>T	p.His128His	synonymous	Exon 5 of 8	ENSP00000363597.2	Q5JT25-1
	RAB41	ENST00000276066.4	TSL:1	c.381C>T	p.His127His	synonymous	Exon 5 of 8	ENSP00000276066.4	Q5JT25-2
	PDZD11	ENST00000695560.1		n.*97-1278G>A		intron	N/A	ENSP00000512017.1	Q5EBL8-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000164 AC: 3 AN: 183382 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000367

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000548 AC: 6 AN: 1095536 Hom.: 0 Cov.: 29 AF XY: 0.00000554 AC XY: 2 AN XY: 360982

African (AFR) AF: 0.00 AC: 0 AN: 26343

American (AMR) AF: 0.00 AC: 0 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19366

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30195

South Asian (SAS) AF: 0.00 AC: 0 AN: 54093

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4126

European-Non Finnish (NFE) AF: 0.00000476 AC: 4 AN: 839657

Other (OTH) AF: 0.0000217 AC: 1 AN: 46022

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.88
DANN	Benign	0.76
PhyloP100		-0.62
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: rs141218284; hg19: chrX-69503403;