Variant X-102937494-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001031834.1(RAB40AL):c.176A>G(p.Asp59Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00557 in 1,210,129 control chromosomes in the GnomAD database, including 18 homozygotes. There are 2,285 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0041 ( 2 hom., 150 hem., cov: 22)

Exomes 𝑓: 0.0057 ( 16 hom. 2135 hem. )

Consequence

RAB40AL
NM_001031834.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 3.12

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013548255).

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB40AL	NM_001031834.1 linkuse as main transcript	c.176A>G	p.Asp59Gly	missense_variant	1/1	ENST00000218249.7	NP_001027004.1
LINC00630	NR_146589.1 linkuse as main transcript	n.1910-21154A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB40AL	ENST00000218249.7 linkuse as main transcript	c.176A>G	p.Asp59Gly	missense_variant	1/1		NM_001031834.1	ENSP00000218249	P1

Frequencies

GnomAD3 genomes

AF:

0.00409

AC:

457

AN:

111842

Hom.:

Cov.:

AF XY:

0.00441

AC XY:

150

AN XY:

34014

show subpopulations

Gnomad AFR

AF:

0.000554

Gnomad AMI

AF:

0.00293

Gnomad AMR

AF:

0.00357

Gnomad ASJ

AF:

0.0348

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00267

Gnomad FIN

AF:

0.00145

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.00527

Gnomad OTH

AF:

0.00732

GnomAD3 exomes

AF:

0.00539

AC:

989

AN:

183454

Hom.:

AF XY:

0.00575

AC XY:

390

AN XY:

67884

show subpopulations

Gnomad AFR exome

AF:

0.000228

Gnomad AMR exome

AF:

0.00233

Gnomad ASJ exome

AF:

0.0348

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00440

Gnomad FIN exome

AF:

0.00156

Gnomad NFE exome

AF:

0.00635

Gnomad OTH exome

AF:

0.00729

GnomAD4 exome

AF:

0.00572

AC:

6278

AN:

1098235

Hom.:

Cov.:

AF XY:

0.00587

AC XY:

2135

AN XY:

363589

show subpopulations

Gnomad4 AFR exome

AF:

0.000871

Gnomad4 AMR exome

AF:

0.00207

Gnomad4 ASJ exome

AF:

0.0340

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00375

Gnomad4 FIN exome

AF:

0.00192

Gnomad4 NFE exome

AF:

0.00583

Gnomad4 OTH exome

AF:

0.00618

GnomAD4 genome

AF:

0.00408

AC:

457

AN:

111894

Hom.:

Cov.:

AF XY:

0.00440

AC XY:

150

AN XY:

34076

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.00356

Gnomad4 ASJ

AF:

0.0348

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00268

Gnomad4 FIN

AF:

0.00145

Gnomad4 NFE

AF:

0.00527

Gnomad4 OTH

AF:

0.00723

Alfa

AF:

0.00555

Hom.:

Bravo

AF:

0.00404

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.00479

AC:

581

EpiCase

AF:

0.00665

EpiControl

AF:

0.00777

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Deafness-intellectual disability, Martin-Probst type syndrome

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Oct 01, 2014

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.0092

MetaRNN

Benign

0.014

MetaSVM

Uncertain

-0.12

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.55

Sift

Pathogenic

0.0

Sift4G

Benign

0.16

Polyphen

1.0

Vest4

0.11

MVP

0.95

MPC

1.4

ClinPred

0.053

GERP RS

0.78

Varity_R

0.87

gMVP

0.82

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