X-70283553-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001363807.1(RAB41):c.384C>T(p.His128=) 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

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 Benign. Variant got -7 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 id is 2660812.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.622 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB41	NM_001363807.1	c.384C>T	p.His128=	synonymous_variant	5/8	ENST00000374473.6
RAB41	NM_001032726.3	c.381C>T	p.His127=	synonymous_variant	5/8
RAB41	XM_011530948.4	c.384C>T	p.His128=	synonymous_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB41	ENST00000374473.6	c.384C>T	p.His128=	synonymous_variant	5/8	5	NM_001363807.1	P1
RAB41	ENST00000276066.4	c.381C>T	p.His127=	synonymous_variant	5/8	1
PDZD11	ENST00000695560.1	c.*97-1278G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.0000164 AC: 3 AN: 183382 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67822

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 SAS 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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000331

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000476

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

RAB41: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	0.88
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs141218284; hg19: chrX-69503403;