dbSNP rs763629323: RAB40A:p.Arg99Leu (chrX-103500461-C-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_080879.3(RAB40A):c.296G>T(p.Arg99Leu) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000082 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

RAB40A
NM_080879.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.27

Publications

2 publications found

Variant links:

Genes affected

RAB40A (HGNC:18283): (RAB40A, member RAS oncogene family) 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. [provided by RefSeq, Apr 2010]

RAB40A links:

LL0XNC01-250H12.3 (HGNC:):

LL0XNC01-250H12.3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.4089924).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080879.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAB40A	NM_080879.3	MANE Select	c.296G>T	p.Arg99Leu	missense	Exon 3 of 3	NP_543155.2	Q8WXH6
LL0XNC01-250H12.3	NR_188433.1		n.2131C>A		non_coding_transcript_exon	Exon 9 of 9
LL0XNC01-250H12.3	NR_188435.1		n.2058C>A		non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAB40A	ENST00000304236.2	TSL:2 MANE Select	c.296G>T	p.Arg99Leu	missense	Exon 3 of 3	ENSP00000305648.1	Q8WXH6
RAB40A	ENST00000372633.1	TSL:6	c.296G>T	p.Arg99Leu	missense	Exon 1 of 1	ENSP00000361716.1	Q8WXH6
RAB40A	ENST00000905301.1		c.296G>T	p.Arg99Leu	missense	Exon 4 of 4	ENSP00000575360.1

Frequencies

GnomAD3 genomes

AF:

0.0000272

AC:

AN:

110362

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000329

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000191

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

GnomAD2 exomes

AF:

0.0000329

AC:

AN:

182140

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000219

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000820

AC:

AN:

1097869

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363287

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26395

American (AMR)

AF:

0.000256

AC:

AN:

35198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19379

East Asian (EAS)

AF:

0.00

AC:

AN:

30196

South Asian (SAS)

AF:

0.00

AC:

AN:

54142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40525

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841815

Other (OTH)

AF:

0.00

AC:

AN:

46087

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000272

AC:

AN:

110362

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32588

show subpopulations

African (AFR)

AF:

0.0000329

AC:

AN:

30372

American (AMR)

AF:

0.000191

AC:

AN:

10460

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2626

East Asian (EAS)

AF:

0.00

AC:

AN:

3522

South Asian (SAS)

AF:

0.00

AC:

AN:

2546

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5932

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52523

Other (OTH)

AF:

0.00

AC:

AN:

1464

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.022

MetaRNN

Benign

0.41

MetaSVM

Uncertain

-0.21

MutationAssessor

Benign

1.4

PhyloP100

5.3

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-5.1

REVEL

Uncertain

0.44

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.015

Varity_R

0.71

gMVP

0.80

Mutation Taster

=98/2

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over