3-129091125-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):ā€‹c.610A>Gā€‹(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 (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 29)
Exomes š‘“: 0.000022 ( 0 hom. )

Consequence

RAB43
NM_198490.3 missense

Scores

19

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]
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]

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
RAB43NM_198490.3 linkc.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
RAB43ENST00000315150.10 linkc.610A>G p.Ile204Val missense_variant 3/31 NM_198490.3 ENSP00000319781.6 Q86YS6-1
ISY1-RAB43ENST00000418265 linkc.*261A>G 3_prime_UTR_variant 13/132 ENSP00000411822.1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152016
Hom.:
0
Cov.:
29
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:
3
AN:
206210
Hom.:
0
AF XY:
0.0000177
AC XY:
2
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:
32
AN:
1445338
Hom.:
0
Cov.:
29
AF XY:
0.0000223
AC XY:
16
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:
3
AN:
152134
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
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:
2

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 submitterclinical testingAmbry GeneticsDec 15, 2023This 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
T
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
N
LIST_S2
Benign
0.74
.;.;.;.;T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.021
T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
-0.20
N;N;N;N;N
PrimateAI
Benign
0.26
T
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
T
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.

Other links and lift over

dbSNP: rs764537903; hg19: chr3-128809968; API