19-18201778-T-C

Variant names:

• chr19-18201778-T-C
• rs17683539
• NM_002866.5:c.228+735A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002866.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB3A	NM_002866.5	MANE Select	c.228+735A>G		intron	N/A	NP_002857.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB3A	ENST00000222256.9	TSL:1 MANE Select	c.228+735A>G		intron	N/A	ENSP00000222256.3
	RAB3A	ENST00000464076.3	TSL:2	c.-57-1333A>G		intron	N/A	ENSP00000474603.1
	RAB3A	ENST00000481914.2	TSL:3	c.228+735A>G		intron	N/A	ENSP00000472335.1

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

African (AFR) AF: 0.215 AC: 8873 AN: 41300

American (AMR) AF: 0.268 AC: 4091 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 864 AN: 3472

East Asian (EAS) AF: 0.101 AC: 519 AN: 5150

South Asian (SAS) AF: 0.166 AC: 797 AN: 4806

European-Finnish (FIN) AF: 0.475 AC: 4984 AN: 10494

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23206 AN: 67894

Other (OTH) AF: 0.281 AC: 591 AN: 2106

Alfa AF: 0.312 Hom.: 19031

Bravo AF: 0.273

Asia WGS AF: 0.149 AC: 518 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	1.9
DANN	Benign	0.82
PhyloP100		-0.65
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: rs17683539; hg19: chr19-18312588;