rs2662389

Positions:

• chr5-58830519-A-C
• chr5-58830519-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB3C	NM_138453.4	c.496+5357A>C		intron_variant		ENST00000282878.6	NP_612462.1
RAB3C	NM_001317915.2	c.490+5357A>C		intron_variant			NP_001304844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB3C	ENST00000282878.6	c.496+5357A>C		intron_variant		1	NM_138453.4	ENSP00000282878	P1
RAB3C	ENST00000381158.3	n.219+5357A>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.546

Alfa AF: 0.444 Hom.: 1888

Bravo AF: 0.552

Asia WGS AF: 0.419 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

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