19-18201778-T-C

Position:

• chr19-18201778-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002866.5(RAB3A):​c.228+735A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,666 control chromosomes in the GnomAD database, including 6,928 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 0.29 (6928 hom., cov: 32)
• Consequence: RAB3A NM_002866.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646

Genes affected

RAB3A (HGNC:9777): (RAB3A, member RAS oncogene family) Enables GTPase activity and myosin V binding activity. Involved in several processes, including acrosomal vesicle exocytosis; lysosome localization; and plasma membrane repair. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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 (NFE) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB3A	NM_002866.5	c.228+735A>G		intron_variant		ENST00000222256.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB3A	ENST00000222256.9	c.228+735A>G		intron_variant		1	NM_002866.5	P1
RAB3A	ENST00000464076.3	c.-57-1333A>G		intron_variant		2
RAB3A	ENST00000481914.2	c.228+735A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44301 AN: 151548 Hom.: 6925 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.292 AC: 44324 AN: 151666 Hom.: 6928 Cov.: 32 AF XY: 0.293 AC XY: 21680 AN XY: 74062

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.281

Alfa AF: 0.320 Hom.: 12175

Bravo AF: 0.273

Asia WGS AF: 0.149 AC: 518 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	1.9
DANN	Benign	0.82

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: rs17683539; hg19: chr19-18312588;