Variant X-70284588-CG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PVS1_ModerateBP6_ModerateBS1BS2

The NM_001363807.1(RAB41):c.616delG(p.Val206fs) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,206,360 control chromosomes in the GnomAD database, including 7 homozygotes. There are 305 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0057 ( 6 hom., 168 hem., cov: 22)

Exomes 𝑓: 0.00053 ( 1 hom. 137 hem. )

Consequence

RAB41
NM_001363807.1 frameshift, splice_region

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.127

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0792 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BP6

Variant X-70284588-CG-C is Benign according to our data. Variant chrX-70284588-CG-C is described in ClinVar as [Benign]. Clinvar id is 714927.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00568 (634/111697) while in subpopulation AFR AF= 0.0192 (590/30715). AF 95% confidence interval is 0.0179. There are 6 homozygotes in gnomad4. There are 168 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB41	NM_001363807.1 link	c.616delG	p.Val206fs	frameshift_variant, splice_region_variant	8/8	ENST00000374473.6	NP_001350736.1
RAB41	NM_001032726.3 link	c.613delG	p.Val205fs	frameshift_variant, splice_region_variant	8/8		NP_001027898.2	Q5JT25-2
RAB41	XM_011530948.4 link	c.*154delG		3_prime_UTR_variant	7/7		XP_011529250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RAB41	ENST00000374473.6 link	c.616delG	p.Val206fs	frameshift_variant, splice_region_variant	8/8	5	NM_001363807.1	ENSP00000363597.2	Q5JT25-1
RAB41	ENST00000276066.4 link	c.613delG	p.Val205fs	frameshift_variant, splice_region_variant	8/8	1		ENSP00000276066.4	Q5JT25-2
PDZD11	ENST00000695561.1 link	n.3337delC		non_coding_transcript_exon_variant	6/6
PDZD11	ENST00000695560.1 link	n.*97-2314delC		intron_variant				ENSP00000512017.1	Q5EBL8-1

Frequencies

GnomAD3 genomes

AF:

0.00568

AC:

634

AN:

111644

Hom.:

Cov.:

AF XY:

0.00497

AC XY:

168

AN XY:

33836

show subpopulations

Gnomad AFR

AF:

0.0193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00305

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000375

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000752

Gnomad OTH

AF:

0.00469

GnomAD3 exomes

AF:

0.00168

AC:

308

AN:

183392

Hom.:

AF XY:

0.000885

AC XY:

AN XY:

67832

show subpopulations

Gnomad AFR exome

AF:

0.0210

Gnomad AMR exome

AF:

0.000802

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:

0.0000366

Gnomad OTH exome

AF:

0.00155

GnomAD4 exome

AF:

0.000525

AC:

575

AN:

1094663

Hom.:

Cov.:

AF XY:

0.000380

AC XY:

137

AN XY:

360165

show subpopulations

Gnomad4 AFR exome

AF:

0.0185

Gnomad4 AMR exome

AF:

0.000767

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:

0.00000834

Gnomad4 OTH exome

AF:

0.00104

GnomAD4 genome

AF:

0.00568

AC:

634

AN:

111697

Hom.:

Cov.:

AF XY:

0.00496

AC XY:

168

AN XY:

33897

show subpopulations

Gnomad4 AFR

AF:

0.0192

Gnomad4 AMR

AF:

0.00304

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000376

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000753

Gnomad4 OTH

AF:

0.00464

Alfa

AF:

0.000882

Hom.:

Bravo

AF:

0.00654

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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