Variant X-102937427-G-A 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.109G>A(p.Gly37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,210,019 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 68 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.00016 ( 0 hom. 64 hem. )

Consequence

RAB40AL
NM_001031834.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.11

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=0.013803482).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB40AL	NM_001031834.1 linkuse as main transcript	c.109G>A	p.Gly37Ser	missense_variant	1/1	ENST00000218249.7	NP_001027004.1	P0C0E4
LINC00630	NR_146589.1 linkuse as main transcript	n.1910-21221G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB40AL	ENST00000218249.7 linkuse as main transcript	c.109G>A	p.Gly37Ser	missense_variant	1/1	6	NM_001031834.1	ENSP00000218249.5		P0C0E4

Frequencies

GnomAD3 genomes

AF:

0.000161

AC:

AN:

111736

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33896

show subpopulations

Gnomad AFR

AF:

0.000196

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:

0.00180

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000234

AC:

AN:

183494

Hom.:

AF XY:

0.000236

AC XY:

AN XY:

67922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00212

Gnomad NFE exome

AF:

0.000110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000160

AC:

176

AN:

1098234

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

AN XY:

363588

show subpopulations

Gnomad4 AFR exome

AF:

0.000189

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00227

Gnomad4 NFE exome

AF:

0.0000891

Gnomad4 OTH exome

AF:

0.0000868

GnomAD4 genome

AF:

0.000161

AC:

AN:

111785

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33955

show subpopulations

Gnomad4 AFR

AF:

0.000195

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00180

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000985

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000206

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

Oct 24, 2024

The c.109G>A (p.G37S) 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 109, causing the glycine (G) at amino acid position 37 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

0.090

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

FATHMM_MKL

Benign

0.61

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.016

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.50

MutationAssessor

Benign

0.68

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.38

Sift

Benign

0.14

Sift4G

Benign

0.18

Polyphen

0.97

Vest4

0.10

MVP

0.96

MPC

0.58

ClinPred

0.16

GERP RS

0.99

Varity_R

0.17

gMVP

0.70

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