rs10065350

Variant names:

• chr5-58786896-C-T
• rs10065350
• NM_138453.4:c.372-38142C>T

Variant summary

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

The NM_138453.4(RAB3C):​c.372-38142C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 152,024 control chromosomes in the GnomAD database, including 847 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 0.093 (847 hom., cov: 31)
• Consequence: RAB3C NM_138453.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172
• Publications: 3 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]

ENSG00000248475 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB3C	NM_138453.4	c.372-38142C>T		intron_variant	Intron 3 of 4	ENST00000282878.6	NP_612462.1
RAB3C	NM_001317915.2	c.366-38142C>T		intron_variant	Intron 3 of 4		NP_001304844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB3C	ENST00000282878.6	c.372-38142C>T		intron_variant	Intron 3 of 4	1	NM_138453.4	ENSP00000282878.4
RAB3C	ENST00000507977.1	n.349-7394C>T		intron_variant	Intron 4 of 4	3
ENSG00000248475	ENST00000509476.1	n.221+27764G>A		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0930 AC: 14124 AN: 151906 Hom.: 843 Cov.: 31

Gnomad AFR AF: 0.0246

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0869

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0769

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0715

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.0930 AC: 14137 AN: 152024 Hom.: 847 Cov.: 31 AF XY: 0.0885 AC XY: 6573 AN XY: 74308

African (AFR) AF: 0.0245 AC: 1017 AN: 41486

American (AMR) AF: 0.0870 AC: 1329 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3472

East Asian (EAS) AF: 0.0770 AC: 398 AN: 5166

South Asian (SAS) AF: 0.105 AC: 507 AN: 4806

European-Finnish (FIN) AF: 0.0715 AC: 757 AN: 10582

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9415 AN: 67922

Other (OTH) AF: 0.112 AC: 236 AN: 2110

Alfa AF: 0.110 Hom.: 702

Bravo AF: 0.0909

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
DANN	Benign	0.95
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10065350; hg19: chr5-58082723;