Variant X-102937387-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001031834.1(RAB40AL):c.69G>C(p.Arg23Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 111,388 control chromosomes in the GnomAD database, including 2,614 homozygotes. There are 4,854 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2614 hom., 4854 hem., cov: 23)

Exomes 𝑓: 0.042 ( 4476 hom. 18555 hem. )

Failed GnomAD Quality Control

Consequence

RAB40AL
NM_001031834.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.339

Variant links:

Genes affected

RAB40AL (HGNC:25410): (RAB40A like) This gene encodes a member of the Rab40 subfamily of Rab small GTP-binding proteins that contains a C-terminal suppressors of cytokine signaling box. Disruptions in this gene are associated with Duchenne muscular dystrophy. [provided by RefSeq, Apr 2010]

RAB40AL links:

LINC00630 (HGNC:):

LINC00630 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.156066E-4).

BP6

Variant X-102937387-G-C is Benign according to our data. Variant chrX-102937387-G-C is described in ClinVar as [Benign]. Clinvar id is 810916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB40AL	NM_001031834.1 linkuse as main transcript	c.69G>C	p.Arg23Ser	missense_variant	1/1	ENST00000218249.7
LINC00630	NR_146589.1 linkuse as main transcript	n.1910-21261G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB40AL	ENST00000218249.7 linkuse as main transcript	c.69G>C	p.Arg23Ser	missense_variant	1/1		NM_001031834.1	P1

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

17050

AN:

111336

Hom.:

2610

Cov.:

AF XY:

0.144

AC XY:

4831

AN XY:

33602

show subpopulations

Gnomad AFR

AF:

0.468

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0764

Gnomad ASJ

AF:

0.0129

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.348

Gnomad FIN

AF:

0.00665

Gnomad MID

AF:

0.0168

Gnomad NFE

AF:

0.00604

Gnomad OTH

AF:

0.113

GnomAD3 exomes

AF:

0.0845

AC:

15196

AN:

179873

Hom.:

1727

AF XY:

0.0883

AC XY:

5914

AN XY:

67003

show subpopulations

Gnomad AFR exome

AF:

0.468

Gnomad AMR exome

AF:

0.0466

Gnomad ASJ exome

AF:

0.0130

Gnomad EAS exome

AF:

0.141

Gnomad SAS exome

AF:

0.317

Gnomad FIN exome

AF:

0.00689

Gnomad NFE exome

AF:

0.00450

Gnomad OTH exome

AF:

0.0481

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0423

AC:

46446

AN:

1097643

Hom.:

4476

Cov.:

AF XY:

0.0511

AC XY:

18555

AN XY:

363387

show subpopulations

Gnomad4 AFR exome

AF:

0.491

Gnomad4 AMR exome

AF:

0.0610

Gnomad4 ASJ exome

AF:

0.0143

Gnomad4 EAS exome

AF:

0.181

Gnomad4 SAS exome

AF:

0.322

Gnomad4 FIN exome

AF:

0.00859

Gnomad4 NFE exome

AF:

0.00519

Gnomad4 OTH exome

AF:

0.0739

GnomAD4 genome

AF:

0.153

AC:

17081

AN:

111388

Hom.:

2614

Cov.:

AF XY:

0.144

AC XY:

4854

AN XY:

33664

show subpopulations

Gnomad4 AFR

AF:

0.468

Gnomad4 AMR

AF:

0.0763

Gnomad4 ASJ

AF:

0.0129

Gnomad4 EAS

AF:

0.167

Gnomad4 SAS

AF:

0.344

Gnomad4 FIN

AF:

0.00665

Gnomad4 NFE

AF:

0.00605

Gnomad4 OTH

AF:

0.119

Alfa

AF:

0.0720

Hom.:

625

Bravo

AF:

0.173

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00554

AC:

ESP6500AA

AF:

0.429

AC:

1646

ESP6500EA

AF:

0.00461

AC:

ExAC

AF:

0.102

AC:

12410

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

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Sep 13, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.11

DANN

Benign

0.62

DEOGEN2

Benign

0.063

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.68

MetaRNN

Benign

0.00032

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

3.9

REVEL

Benign

0.17

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.054

MutPred

0.63

Gain of phosphorylation at R23 (P = 0.055);

MPC

0.50

ClinPred

0.0000096

GERP RS

-0.0052

Varity_R

0.14

gMVP

0.75

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