Variant 3-19978394-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004162.5(RAB5A):c.523A>G(p.Met175Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000318 in 1,573,258 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RAB5A
NM_004162.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.98

Variant links:

Genes affected

RAB5A (HGNC:9783): (RAB5A, member RAS oncogene family) Enables GDP binding activity; GTP binding activity; and GTPase activity. Involved in several processes, including amyloid-beta clearance by transcytosis; early endosome to late endosome transport; and regulation of exocytosis. Located in several cellular components, including cytoplasmic side of early endosome membrane; nucleoplasm; and terminal bouton. [provided by Alliance of Genome Resources, Apr 2022]

RAB5A links:

RAB5A (HGNC:):

RAB5A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB5A	NM_004162.5 linkuse as main transcript	c.523A>G	p.Met175Val	missense_variant	5/6	ENST00000273047.9	NP_004153.2	P20339-1A0A024R2K1
RAB5A	NM_001292048.2 linkuse as main transcript	c.481A>G	p.Met161Val	missense_variant	5/6		NP_001278977.1	P20339-2
RAB5A	XM_047448648.1 linkuse as main transcript	c.262A>G	p.Met88Val	missense_variant	5/6		XP_047304604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB5A	ENST00000273047.9 linkuse as main transcript	c.523A>G	p.Met175Val	missense_variant	5/6	1	NM_004162.5	ENSP00000273047.4		P20339-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.00000400

AC:

AN:

250142

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135252

show subpopulations

Gnomad AFR exome

AF:

0.0000617

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000211

AC:

AN:

1421038

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

709452

show subpopulations

Gnomad4 AFR exome

AF:

0.0000308

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:

0.00

Gnomad4 NFE exome

AF:

0.00000186

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000482

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

Bravo

AF:

0.00000378

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 01, 2024

The c.523A>G (p.M175V) alteration is located in exon 5 (coding exon 4) of the RAB5A gene. This alteration results from a A to G substitution at nucleotide position 523, causing the methionine (M) at amino acid position 175 to be replaced by a valine (V). 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

0.14

BayesDel_addAF

Uncertain

0.044

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.32

T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.50

D;D

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.18

N;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.28

Sift

Benign

0.49

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.0

B;.

Vest4

0.70

MVP

0.92

MPC

0.48

ClinPred

0.20

GERP RS

5.6

Varity_R

0.37

gMVP

0.61

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