rs2342285

Variant names:

• chr3-129096551-C-T
• rs2342285
• NM_198490.3:c.205-1382G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_198490.3(RAB43):​c.205-1382G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00722 in 152,204 control chromosomes in the GnomAD database, including 7 homozygotes. 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: 𝑓 0.0072 (7 hom., cov: 32)
• Consequence: RAB43 NM_198490.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.701
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00722 (1099/152204) while in subpopulation AFR AF = 0.0201 (834/41522). AF 95% confidence interval is 0.019. There are 7 homozygotes in GnomAd4. There are 515 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198490.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB43	NM_198490.3	MANE Select	c.205-1382G>A		intron	N/A	NP_940892.1
	ISY1-RAB43	NM_001204890.2		c.852-1382G>A		intron	N/A	NP_001191819.1
	RAB43	NM_001204883.2		c.205-1382G>A		intron	N/A	NP_001191812.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB43	ENST00000315150.10	TSL:1 MANE Select	c.205-1382G>A		intron	N/A	ENSP00000319781.6
	ISY1-RAB43	ENST00000418265.1	TSL:2	c.852-1382G>A		intron	N/A	ENSP00000411822.1
	RAB43	ENST00000393304.5	TSL:4	c.205-1382G>A		intron	N/A	ENSP00000376981.1

Frequencies

GnomAD3 genomes AF: 0.00714 AC: 1086 AN: 152086 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00472

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00198

Gnomad OTH AF: 0.00623

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

GnomAD4 genome AF: 0.00722 AC: 1099 AN: 152204 Hom.: 7 Cov.: 32 AF XY: 0.00692 AC XY: 515 AN XY: 74418

African (AFR) AF: 0.0201 AC: 834 AN: 41522

American (AMR) AF: 0.00471 AC: 72 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00622 AC: 30 AN: 4822

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00199 AC: 135 AN: 68008

Other (OTH) AF: 0.00616 AC: 13 AN: 2110

Alfa AF: 0.00634 Hom.: 2

Bravo AF: 0.00818

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.4
DANN	Benign	0.67
PhyloP100		0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs2342285; hg19: chr3-128815394;