3-129091125-T-C

Position:

chr3-129091125-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_198490.3(RAB43):c.610A>G(p.Ile204Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,597,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

RAB43
NM_198490.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.296

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020713508).

BP6

Variant 3-129091125-T-C is Benign according to our data. Variant chr3-129091125-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3150803.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB43	NM_198490.3 link	c.610A>G	p.Ile204Val	missense_variant	3/3	ENST00000315150.10	NP_940892.1	Q86YS6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB43	ENST00000315150.10 link	c.610A>G	p.Ile204Val	missense_variant	3/3	1	NM_198490.3	ENSP00000319781.6		Q86YS6-1
ISY1-RAB43	ENST00000418265 link	c.*261A>G		3_prime_UTR_variant	13/13	2		ENSP00000411822.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152016

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:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000145

AC:

AN:

206210

Hom.:

AF XY:

0.0000177

AC XY:

AN XY:

113060

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000340

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:

0.0000220

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000221

AC:

AN:

1445338

Hom.:

Cov.:

AF XY:

0.0000223

AC XY:

AN XY:

718508

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000711

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000226

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000442

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

ExAC

AF:

0.0000167

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.041

DANN

Benign

0.68

DEOGEN2

Benign

0.0073

T;T;T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.74

.;.;.;.;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.021

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.20

N;N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

0.37

N;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

B;B;B;B;B

Vest4

0.041

MutPred

0.26

Gain of disorder (P = 0.1763);Gain of disorder (P = 0.1763);Gain of disorder (P = 0.1763);Gain of disorder (P = 0.1763);Gain of disorder (P = 0.1763);

MVP

0.40

MPC

1.2

ClinPred

0.011

GERP RS

-5.1

Varity_R

0.017

gMVP

0.22

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