chr3-129118310-T-C

Variant names:

• chr3-129118310-T-C
• rs1021123
• NM_198490.3:c.204+2976A>G

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+2976A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00567 in 152,330 control chromosomes in the GnomAD database, including 3 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 0.0057 (3 hom., cov: 32)
• Consequence: RAB43 NM_198490.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248
• 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=-0.88).
• BS2: High Homozygotes in GnomAd4 at 3 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB43	NM_198490.3	MANE Select	c.204+2976A>G		intron	N/A	NP_940892.1	Q86YS6-1
	ISY1-RAB43	NM_001204890.2		c.851+11778A>G		intron	N/A	NP_001191819.1
	RAB43	NM_001204883.2		c.204+2976A>G		intron	N/A	NP_001191812.1	Q86YS6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB43	ENST00000315150.10	TSL:1 MANE Select	c.204+2976A>G		intron	N/A	ENSP00000319781.6	Q86YS6-1
	ISY1-RAB43	ENST00000418265.1	TSL:2	c.851+11778A>G		intron	N/A	ENSP00000411822.1
	RAB43	ENST00000915979.1		c.204+2976A>G		intron	N/A	ENSP00000586038.1

Frequencies

GnomAD3 genomes AF: 0.00564 AC: 859 AN: 152212 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0147

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: 0.00567 AC: 863 AN: 152330 Hom.: 3 Cov.: 32 AF XY: 0.00541 AC XY: 403 AN XY: 74490

African (AFR) AF: 0.0148 AC: 614 AN: 41566

American (AMR) AF: 0.00431 AC: 66 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

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: 68034

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

Alfa AF: 0.00473 Hom.: 0

Bravo AF: 0.00648

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.67
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1021123; hg19: chr3-128837153;