Variant X-102937376-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001031834.1(RAB40AL):c.58G>A(p.Val20Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,210,262 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.000017 ( 0 hom. 4 hem. )

Consequence

RAB40AL
NM_001031834.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB40AL	NM_001031834.1 linkuse as main transcript	c.58G>A	p.Val20Met	missense_variant	1/1	ENST00000218249.7
LINC00630	NR_146589.1 linkuse as main transcript	n.1910-21272G>A		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.58G>A	p.Val20Met	missense_variant	1/1		NM_001031834.1	P1

Frequencies

GnomAD3 genomes

AF:

0.000179

AC:

AN:

112006

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34156

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000382

AC:

AN:

183078

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67546

show subpopulations

Gnomad AFR exome

AF:

0.000460

Gnomad AMR exome

AF:

0.0000365

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000173

AC:

AN:

1098205

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

363563

show subpopulations

Gnomad4 AFR exome

AF:

0.000606

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.000178

AC:

AN:

112057

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34217

show subpopulations

Gnomad4 AFR

AF:

0.000649

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000170

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.58G>A (p.V20M) alteration is located in exon 1 (coding exon 1) of the RAB40AL gene. This alteration results from a G to A substitution at nucleotide position 58, causing the valine (V) at amino acid position 20 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.12

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.33

FATHMM_MKL

Benign

0.58

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.46

MetaSVM

Uncertain

0.11

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.58

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.45

MVP

0.96

MPC

1.3

ClinPred

0.19

GERP RS

0.99

Varity_R

0.55

gMVP

0.74

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