rs2128342

Variant names:

• chr3-129114785-G-A
• rs2128342
• NM_198490.3:c.204+6501C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_198490.3(RAB43):​c.204+6501C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00563 in 152,292 control chromosomes in the GnomAD database, including 2 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 0.0056 (2 hom., cov: 31)
• Consequence: RAB43 NM_198490.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB43	NM_198490.3	c.204+6501C>T		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.204+6501C>T		intron_variant	Intron 1 of 2	1	NM_198490.3	ENSP00000319781.6
ISY1-RAB43	ENST00000418265.1	c.851+15303C>T		intron_variant	Intron 11 of 12	2		ENSP00000411822.1

Frequencies

GnomAD3 genomes AF: 0.00561 AC: 854 AN: 152174 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00190

Gnomad OTH AF: 0.00573

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

GnomAD4 genome AF: 0.00563 AC: 858 AN: 152292 Hom.: 2 Cov.: 31 AF XY: 0.00538 AC XY: 401 AN XY: 74470

African (AFR) AF: 0.0147 AC: 609 AN: 41538

American (AMR) AF: 0.00432 AC: 66 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4826

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00190 AC: 129 AN: 68038

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00431 Hom.: 0

Bravo AF: 0.00648

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.48
PhyloP100		0.28
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: rs2128342; hg19: chr3-128833628;