chr5-58830519-A-C

Variant names:

• chr5-58830519-A-C
• rs2662389
• NM_138453.4:c.496+5357A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138453.4(RAB3C):​c.496+5357A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,958 control chromosomes in the GnomAD database, including 23,499 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 0.55 (23499 hom., cov: 31)
• Consequence: RAB3C NM_138453.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 2 publications found

Genes affected

RAB3C (HGNC:30269): (RAB3C, member RAS oncogene family) This gene is a member of the RAS oncogene family and encodes a small GTPase. Other similar small GTPases are known to be involved in vesicle trafficking, and the encoded protein was shown to play a role in recycling phagocytosed MHC class 1 complexes to the cell surface. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138453.4. 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
	RAB3C	NM_138453.4	MANE Select	c.496+5357A>C		intron	N/A	NP_612462.1
	RAB3C	NM_001317915.2		c.490+5357A>C		intron	N/A	NP_001304844.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB3C	ENST00000282878.6	TSL:1 MANE Select	c.496+5357A>C		intron	N/A	ENSP00000282878.4
	RAB3C	ENST00000381158.3	TSL:3	n.219+5357A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83599 AN: 151842 Hom.: 23489 Cov.: 31

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.550 AC: 83636 AN: 151958 Hom.: 23499 Cov.: 31 AF XY: 0.545 AC XY: 40504 AN XY: 74276

African (AFR) AF: 0.617 AC: 25566 AN: 41412

American (AMR) AF: 0.513 AC: 7830 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2062 AN: 3472

East Asian (EAS) AF: 0.228 AC: 1175 AN: 5162

South Asian (SAS) AF: 0.528 AC: 2540 AN: 4814

European-Finnish (FIN) AF: 0.491 AC: 5171 AN: 10540

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37364 AN: 67976

Other (OTH) AF: 0.546 AC: 1154 AN: 2112

Alfa AF: 0.451 Hom.: 2018

Bravo AF: 0.552

Asia WGS AF: 0.419 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.72
PhyloP100		0.058
Mutation Taster		=100/0	polymorphism (auto)

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: rs2662389; hg19: chr5-58126346; COSMIC: COSV51433600;