3-129107432-G-T

Variant names:

• chr3-129107432-G-T
• rs922834
• NM_198490.3:c.205-12263C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198490.3(RAB43):​c.205-12263C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAB43 NM_198490.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB43	NM_198490.3	c.205-12263C>A		intron_variant	Intron 1 of 2	ENST00000315150.10	NP_940892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB43	ENST00000315150.10	c.205-12263C>A		intron_variant	Intron 1 of 2	1	NM_198490.3	ENSP00000319781.6
ISY1-RAB43	ENST00000418265.1	c.852-12263C>A		intron_variant	Intron 11 of 12	2		ENSP00000411822.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.010
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs922834; hg19: chr3-128826275;