Genetic Variant NM_001031834.1:c.485A>G (chrX-102937803-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001031834.1(RAB40AL):c.485A>G(p.Asn162Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000992 in 1,209,673 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000010 ( 0 hom. 4 hem. )

Consequence

RAB40AL
NM_001031834.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.52

Publications

0 publications found

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:

ENSG00000234050 (HGNC:):

ENSG00000234050 links:

LINC00630 (HGNC:44263): (long intergenic non-protein coding RNA 630)

LINC00630 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB40AL	NM_001031834.1 link	c.485A>G	p.Asn162Ser	missense_variant	Exon 1 of 1	ENST00000218249.7	NP_001027004.1	P0C0E4
LINC00630	NR_146589.1 link	n.1910-20845A>G		intron_variant	Intron 10 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RAB40AL	ENST00000218249.7 link	c.485A>G	p.Asn162Ser	missense_variant	Exon 1 of 1	6	NM_001031834.1	ENSP00000218249.5	P0C0E4
ENSG00000234050	ENST00000413528.1 link	n.595T>C		non_coding_transcript_exon_variant	Exon 2 of 2	5
LINC00630	ENST00000420471.6 link	n.1747+32066A>G		intron_variant	Intron 13 of 13	3

Frequencies

GnomAD3 genomes

AF:

0.00000897

AC:

AN:

111482

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000328

AC:

AN:

183144

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.000153

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000145

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000100

AC:

AN:

1098137

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

363513

show subpopulations

African (AFR)

AF:

0.000152

AC:

AN:

26392

American (AMR)

AF:

0.0000284

AC:

AN:

35199

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19385

East Asian (EAS)

AF:

0.0000993

AC:

AN:

30198

South Asian (SAS)

AF:

0.00

AC:

AN:

54109

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40533

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4131

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

842103

Other (OTH)

AF:

0.0000217

AC:

AN:

46087

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000897

AC:

AN:

111536

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33740

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30439

American (AMR)

AF:

0.00

AC:

AN:

10707

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3495

South Asian (SAS)

AF:

0.00

AC:

AN:

2545

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6159

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53112

Other (OTH)

AF:

0.00

AC:

AN:

1527

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000416

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 14, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.485A>G (p.N162S) alteration is located in exon 1 (coding exon 1) of the RAB40AL gene. This alteration results from a A to G substitution at nucleotide position 485, causing the asparagine (N) at amino acid position 162 to be replaced by a serine (S). 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

Benign

0.20

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

FATHMM_MKL

Uncertain

0.78

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.0072

MetaRNN

Uncertain

0.57

MetaSVM

Uncertain

0.16

MutationAssessor

Uncertain

2.1

PhyloP100

6.5

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-4.6

REVEL

Uncertain

0.41

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.043

Polyphen

0.96

Vest4

0.51

MVP

0.95

MPC

1.1

ClinPred

0.60

GERP RS

0.82

Varity_R

0.59

gMVP

0.47

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over