Genetic Variant RAB5C:p.Ala143Ala (chr17-42128273-G-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004583.4(RAB5C):c.429C>T(p.Ala143Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,612,852 control chromosomes in the GnomAD database, including 28,732 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5237 hom., cov: 32)

Exomes 𝑓: 0.17 ( 23495 hom. )

Consequence

RAB5C
NM_004583.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.569

Variant links:

Genes affected

RAB5C (HGNC:9785): (RAB5C, member RAS oncogene family) Members of the Rab protein family are small GTPases of the Ras superfamily that are thought to ensure fidelity in the process of docking and/or fusion of vesicles with their correct acceptor compartment (Han et al., 1996 [PubMed 8646882]).[supplied by OMIM, Nov 2010]

RAB5C links:

ENSG00000267261 (HGNC:):

ENSG00000267261 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 17-42128273-G-A is Benign according to our data. Variant chr17-42128273-G-A is described in ClinVar as [Benign]. Clinvar id is 1241743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.569 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB5C	NM_004583.4 link	c.429C>T	p.Ala143Ala	synonymous_variant	Exon 4 of 6	ENST00000346213.9	NP_004574.2	P51148-1A0A024R1U4
RAB5C	NM_001252039.2 link	c.528C>T	p.Ala176Ala	synonymous_variant	Exon 5 of 7		NP_001238968.1	P51148-2
RAB5C	NM_201434.3 link	c.429C>T	p.Ala143Ala	synonymous_variant	Exon 5 of 7		NP_958842.1	P51148-1A0A024R1U4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB5C	ENST00000346213.9 link	c.429C>T	p.Ala143Ala	synonymous_variant	Exon 4 of 6	1	NM_004583.4	ENSP00000345689.5		P51148-1
ENSG00000267261	ENST00000592574.1 link	c.429C>T	p.Ala143Ala	synonymous_variant	Exon 4 of 8	5		ENSP00000468367.1		K7ERQ8

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36368

AN:

151996

Hom.:

5233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.410

Gnomad AMI

AF:

0.306

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.216

GnomAD3 exomes

AF:

0.182

AC:

45468

AN:

250232

Hom.:

4761

AF XY:

0.179

AC XY:

24203

AN XY:

135236

show subpopulations

Gnomad AFR exome

AF:

0.408

Gnomad AMR exome

AF:

0.118

Gnomad ASJ exome

AF:

0.151

Gnomad EAS exome

AF:

0.149

Gnomad SAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.204

Gnomad NFE exome

AF:

0.175

Gnomad OTH exome

AF:

0.167

GnomAD4 exome

AF:

0.173

AC:

252935

AN:

1460738

Hom.:

23495

Cov.:

AF XY:

0.172

AC XY:

124884

AN XY:

726672

show subpopulations

Gnomad4 AFR exome

AF:

0.424

Gnomad4 AMR exome

AF:

0.124

Gnomad4 ASJ exome

AF:

0.148

Gnomad4 EAS exome

AF:

0.156

Gnomad4 SAS exome

AF:

0.169

Gnomad4 FIN exome

AF:

0.204

Gnomad4 NFE exome

AF:

0.167

Gnomad4 OTH exome

AF:

0.187

GnomAD4 genome

AF:

0.239

AC:

36396

AN:

152114

Hom.:

5237

Cov.:

AF XY:

0.238

AC XY:

17696

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.410

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.143

Gnomad4 EAS

AF:

0.150

Gnomad4 SAS

AF:

0.178

Gnomad4 FIN

AF:

0.215

Gnomad4 NFE

AF:

0.171

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.205

Hom.:

1904

Bravo

AF:

0.242

EpiCase

AF:

0.167

EpiControl

AF:

0.167

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 05, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

8.4

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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