rs1046565

chr19-18200389-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_002866.5(RAB3A):c.285T>C(p.Ala95=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,613,350 control chromosomes in the GnomAD database, including 81,309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (6190 hom., cov: 32)
  • Exomes 𝑓: 0.31 (75119 hom.)
• Consequence: RAB3A NM_002866.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.23

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 19-18200389-A-G is Benign according to our data. Variant chr19-18200389-A-G is described in ClinVar as [Benign]. Clinvar id is 1335855.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.23 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB3A	NM_002866.5	c.285T>C	p.Ala95=	synonymous_variant	3/5	ENST00000222256.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB3A	ENST00000222256.9	c.285T>C	p.Ala95=	synonymous_variant	3/5	1	NM_002866.5	P1
RAB3A	ENST00000481914.2	c.285T>C	p.Ala95=	synonymous_variant	3/3	3
RAB3A	ENST00000464076.3	c.-1T>C		5_prime_UTR_variant	2/4	2

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38464 AN: 151996 Hom.: 6189 Cov.: 32

Gnomad AFR AF: 0.0695

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.255

GnomAD3 exomes AF: 0.283 AC: 70967 AN: 251108 Hom.: 11616 AF XY: 0.282 AC XY: 38296 AN XY: 135712

Gnomad AFR exome AF: 0.0626

Gnomad AMR exome AF: 0.268

Gnomad ASJ exome AF: 0.259

Gnomad EAS exome AF: 0.102

Gnomad SAS exome AF: 0.174

Gnomad FIN exome AF: 0.463

Gnomad NFE exome AF: 0.344

Gnomad OTH exome AF: 0.293

GnomAD4 exome AF: 0.312 AC: 455802 AN: 1461236 Hom.: 75119 Cov.: 35 AF XY: 0.309 AC XY: 224400 AN XY: 726922

Gnomad4 AFR exome AF: 0.0562

Gnomad4 AMR exome AF: 0.264

Gnomad4 ASJ exome AF: 0.262

Gnomad4 EAS exome AF: 0.102

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.461

Gnomad4 NFE exome AF: 0.335

Gnomad4 OTH exome AF: 0.286

GnomAD4 genome AF: 0.253 AC: 38470 AN: 152114 Hom.: 6190 Cov.: 32 AF XY: 0.254 AC XY: 18896 AN XY: 74356

Gnomad4 AFR AF: 0.0693

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.255

Alfa AF: 0.314 Hom.: 9669

Bravo AF: 0.230

Asia WGS AF: 0.140 AC: 489 AN: 3478

EpiCase AF: 0.331

EpiControl AF: 0.335

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	2.2
Dann	Benign	0.45

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: rs1046565; hg19: chr19-18311199; COSMIC: COSV55852088; COSMIC: COSV55852088;