Variant 3-129121478-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_198490.3(RAB43):c.12G>A(p.Pro4Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 1,610,716 control chromosomes in the GnomAD database, including 951 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.034 ( 207 hom., cov: 33)

Exomes 𝑓: 0.011 ( 744 hom. )

Consequence

RAB43
NM_198490.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0450

Variant links:

Genes affected

RAB43 (HGNC:19983): (RAB43, member RAS oncogene family) Enables GTPase activity. Involved in several processes, including Golgi organization; phagosome maturation; and retrograde transport, plasma membrane to Golgi. Located in Golgi apparatus and phagocytic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

RAB43 links:

ISY1-RAB43 (HGNC:42969): (ISY1-RAB43 readthrough) This locus represents naturally occurring read-through transcription between the neighboring ISY1 (ISY1 splicing factor homolog) and RAB43 (RAB43, member RAS oncogene family) gene on chromosome 3. The read-through transcript encodes a protein that shares sequence identity with the upstream gene product, but its C-terminus is distinct due to a frameshift relative to the downstream gene. [provided by RefSeq, Mar 2011]

ISY1-RAB43 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 3-129121478-C-T is Benign according to our data. Variant chr3-129121478-C-T is described in ClinVar as [Benign]. Clinvar id is 3056372.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.045 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0999 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB43	NM_198490.3 linkuse as main transcript	c.12G>A	p.Pro4Pro	synonymous_variant	1/3	ENST00000315150.10	NP_940892.1	Q86YS6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB43	ENST00000315150.10 linkuse as main transcript	c.12G>A	p.Pro4Pro	synonymous_variant	1/3	1	NM_198490.3	ENSP00000319781.6		Q86YS6-1
ISY1-RAB43	ENST00000418265.1 linkuse as main transcript	c.851+8610G>A		intron_variant		2		ENSP00000411822.1

Frequencies

GnomAD3 genomes

AF:

0.0343

AC:

5224

AN:

152132

Hom.:

206

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0886

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0144

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.0952

Gnomad FIN

AF:

0.0170

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.0278

AC:

6587

AN:

236792

Hom.:

311

AF XY:

0.0290

AC XY:

3769

AN XY:

129858

show subpopulations

Gnomad AFR exome

AF:

0.0892

Gnomad AMR exome

AF:

0.00337

Gnomad ASJ exome

AF:

0.00103

Gnomad EAS exome

AF:

0.116

Gnomad SAS exome

AF:

0.0867

Gnomad FIN exome

AF:

0.0178

Gnomad NFE exome

AF:

0.00125

Gnomad OTH exome

AF:

0.0123

GnomAD4 exome

AF:

0.0115

AC:

16766

AN:

1458468

Hom.:

744

Cov.:

AF XY:

0.0133

AC XY:

9679

AN XY:

725416

show subpopulations

Gnomad4 AFR exome

AF:

0.0945

Gnomad4 AMR exome

AF:

0.00446

Gnomad4 ASJ exome

AF:

0.000960

Gnomad4 EAS exome

AF:

0.0835

Gnomad4 SAS exome

AF:

0.0833

Gnomad4 FIN exome

AF:

0.0166

Gnomad4 NFE exome

AF:

0.000916

Gnomad4 OTH exome

AF:

0.0165

GnomAD4 genome

AF:

0.0343

AC:

5229

AN:

152248

Hom.:

207

Cov.:

AF XY:

0.0361

AC XY:

2691

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0885

Gnomad4 AMR

AF:

0.0144

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.107

Gnomad4 SAS

AF:

0.0948

Gnomad4 FIN

AF:

0.0170

Gnomad4 NFE

AF:

0.00131

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.00768

Hom.:

Bravo

AF:

0.0346

Asia WGS

AF:

0.0830

AC:

287

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RAB43-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 02, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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