Genetic Variant NM_080879.3:c.110G>A (chrX-103500647-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_080879.3(RAB40A):c.110G>A(p.Gly37Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 1,208,390 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000091 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Consequence

RAB40A
NM_080879.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.68

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37749845).

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.110G>A	p.Gly37Asp	missense	Exon 3 of 3	NP_543155.2	Q8WXH6
LL0XNC01-250H12.3	NR_188433.1		n.2317C>T		non_coding_transcript_exon	Exon 9 of 9
LL0XNC01-250H12.3	NR_188435.1		n.2244C>T		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.110G>A	p.Gly37Asp	missense	Exon 3 of 3	ENSP00000305648.1	Q8WXH6
RAB40A	ENST00000372633.1	TSL:6	c.110G>A	p.Gly37Asp	missense	Exon 1 of 1	ENSP00000361716.1	Q8WXH6
RAB40A	ENST00000905301.1		c.110G>A	p.Gly37Asp	missense	Exon 4 of 4	ENSP00000575360.1

Frequencies

GnomAD3 genomes

AF:

0.00000908

AC:

AN:

110180

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:

0.0000190

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000545

AC:

AN:

183518

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000273

AC:

AN:

1098210

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363598

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26403

American (AMR)

AF:

0.00

AC:

AN:

35204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19382

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

54146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40533

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00000356

AC:

AN:

842108

Other (OTH)

AF:

0.00

AC:

AN:

46091

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000908

AC:

AN:

110180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32398

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30178

American (AMR)

AF:

0.00

AC:

AN:

10441

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2625

East Asian (EAS)

AF:

0.00

AC:

AN:

3513

South Asian (SAS)

AF:

0.00

AC:

AN:

2431

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5992

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000190

AC:

AN:

52615

Other (OTH)

AF:

0.00

AC:

AN:

1465

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

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

0.14

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.091

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.010

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.61

MutationAssessor

Benign

-0.28

PhyloP100

2.7

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.41

Sift

Benign

0.52

Sift4G

Benign

0.55

Polyphen

0.99

Vest4

0.30

MutPred

0.49

Gain of solvent accessibility (P = 0.0281)

MVP

0.97

MPC

2.1

ClinPred

0.46

GERP RS

0.49

Varity_R

0.22

gMVP

0.77

Mutation Taster

=99/1

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over