3-129091152-C-T

Variant names:

• chr3-129091152-C-T
• rs767904953
• NM_198490.3:c.583G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198490.3(RAB43):​c.583G>A​(p.Asp195Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000108 in 1,577,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: RAB43 NM_198490.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.37
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13739145).

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.583G>A	p.Asp195Asn	missense	Exon 3 of 3	NP_940892.1	Q86YS6-1
	RAB43	NM_001204883.2		c.583G>A	p.Asp195Asn	missense	Exon 4 of 4	NP_001191812.1	Q86YS6-1
	RAB43	NM_001204884.2		c.583G>A	p.Asp195Asn	missense	Exon 4 of 4	NP_001191813.1	Q86YS6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB43	ENST00000315150.10	TSL:1 MANE Select	c.583G>A	p.Asp195Asn	missense	Exon 3 of 3	ENSP00000319781.6	Q86YS6-1
	ISY1-RAB43	ENST00000418265.1	TSL:2	c.*234G>A		3_prime_UTR	Exon 13 of 13	ENSP00000411822.1
	RAB43	ENST00000915979.1		c.640G>A	p.Asp214Asn	missense	Exon 5 of 5	ENSP00000586038.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151888 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000174 AC: 3 AN: 172460 AF XY: 0.0000321

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000142

Gnomad OTH exome AF: 0.000217

GnomAD4 exome AF: 0.0000112 AC: 16 AN: 1426078 Hom.: 0 Cov.: 27 AF XY: 0.0000127 AC XY: 9 AN XY: 707676

African (AFR) AF: 0.00 AC: 0 AN: 32656

American (AMR) AF: 0.00 AC: 0 AN: 40948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25468

East Asian (EAS) AF: 0.00 AC: 0 AN: 38722

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50912

Middle Eastern (MID) AF: 0.000222 AC: 1 AN: 4506

European-Non Finnish (NFE) AF: 0.0000128 AC: 14 AN: 1090842

Other (OTH) AF: 0.00 AC: 0 AN: 58796

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151888 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 74158

African (AFR) AF: 0.00 AC: 0 AN: 41356

American (AMR) AF: 0.00 AC: 0 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67948

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000168 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.55	N
PhyloP100		4.4
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.13
Sift	Benign	0.64	T
Sift4G	Benign	0.59	T
Polyphen		0.49	P
Vest4		0.29
MutPred		0.19		Gain of sheet (P = 0.1208)
MVP		0.78
MPC		1.6
ClinPred		0.22	T
GERP RS		5.0
Varity_R		0.077
gMVP		0.59
Mutation Taster		=54/46	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: rs767904953; hg19: chr3-128809995;