3-129121369-C-T

Variant names:

• chr3-129121369-C-T
• rs1325328166
• NM_198490.3:c.121G>A

Variant summary

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

The NM_198490.3(RAB43):​c.121G>A​(p.Gly41Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,328 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RAB43 NM_198490.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.27

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]

ACMG classification

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 rank	MANE	Protein	UniProt
RAB43	NM_198490.3	c.121G>A	p.Gly41Ser	missense_variant	Exon 1 of 3	ENST00000315150.10	NP_940892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB43	ENST00000315150.10	c.121G>A	p.Gly41Ser	missense_variant	Exon 1 of 3	1	NM_198490.3	ENSP00000319781.6
ISY1-RAB43	ENST00000418265.1	c.851+8719G>A		intron_variant	Intron 11 of 12	2		ENSP00000411822.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459328 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725744

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.121G>A (p.G41S) alteration is located in exon 1 (coding exon 1) of the RAB43 gene. This alteration results from a G to A substitution at nucleotide position 121, causing the glycine (G) at amino acid position 41 to be replaced by a serine (S). 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	Uncertain	0.34
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D;D;D;D;D;.;.;D
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.50	D
LIST_S2	Uncertain	0.96	.;.;.;.;D;.;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.66	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.057	D
MutationAssessor	Uncertain	2.1	M;M;M;M;M;M;M;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-4.7	D;D;D;D;D;D;.;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.014	D;D;D;D;D;D;.;D
Sift4G	Uncertain	0.045	D;D;D;D;D;D;D;.
Polyphen		1.0	D;D;D;D;D;.;.;.
Vest4		0.48
MutPred		0.49		Gain of disorder (P = 0.0727);Gain of disorder (P = 0.0727);Gain of disorder (P = 0.0727);Gain of disorder (P = 0.0727);Gain of disorder (P = 0.0727);Gain of disorder (P = 0.0727);Gain of disorder (P = 0.0727);Gain of disorder (P = 0.0727);
MVP		0.93
MPC		2.6
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.49
gMVP		0.86

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

Other links and lift over

dbSNP: rs1325328166; hg19: chr3-128840212;