Variant 3-129091202-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198490.3(RAB43):c.533C>T(p.Thr178Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,585,542 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

RAB43
NM_198490.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.41

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 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
RAB43	NM_198490.3 linkuse as main transcript	c.533C>T	p.Thr178Met	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 linkuse as main transcript	c.533C>T	p.Thr178Met	missense_variant	3/3	1	NM_198490.3	ENSP00000319781.6		Q86YS6-1
ISY1-RAB43	ENST00000418265 linkuse as main transcript	c.*184C>T		3_prime_UTR_variant	13/13	2		ENSP00000411822.1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151672

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:

0.0000389

AC:

AN:

205822

Hom.:

AF XY:

0.0000268

AC XY:

AN XY:

111822

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000342

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:

0.0000785

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000377

AC:

AN:

1433870

Hom.:

Cov.:

AF XY:

0.0000379

AC XY:

AN XY:

711480

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000243

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000193

Gnomad4 NFE exome

AF:

0.0000457

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151672

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74030

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

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000166

AC:

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 05, 2022

The c.533C>T (p.T178M) alteration is located in exon 3 (coding exon 3) of the RAB43 gene. This alteration results from a C to T substitution at nucleotide position 533, causing the threonine (T) at amino acid position 178 to be replaced by a methionine (M). 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

0.12

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;T;T;T;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

.;.;.;.;D

M_CAP

Benign

0.064

MetaRNN

Uncertain

0.43

T;T;T;T;T

MetaSVM

Uncertain

-0.18

MutationAssessor

Benign

1.7

L;L;L;L;L

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.5

D;D;D;D;D

REVEL

Uncertain

0.48

Sift

Uncertain

0.025

D;D;D;D;D

Sift4G

Benign

0.090

T;T;T;T;T

Polyphen

0.99

D;D;D;D;D

Vest4

0.38

MutPred

0.51

Gain of solvent accessibility (P = 0.3418);Gain of solvent accessibility (P = 0.3418);Gain of solvent accessibility (P = 0.3418);Gain of solvent accessibility (P = 0.3418);Gain of solvent accessibility (P = 0.3418);

MVP

0.97

MPC

2.6

ClinPred

0.44

GERP RS

5.0

Varity_R

0.099

gMVP

0.51

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