Variant rs1046565 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002866.5(RAB3A):c.285T>C(p.Ala95Ala) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.23

Variant links:

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]

RAB3A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
RAB3A	NM_002866.5 linkuse as main transcript	c.285T>C	p.Ala95Ala	synonymous_variant	3/5	ENST00000222256.9	NP_002857.1	P20336A0A024R7I7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RAB3A	ENST00000222256.9 linkuse as main transcript	c.285T>C	p.Ala95Ala	synonymous_variant	3/5	1	NM_002866.5	ENSP00000222256.3	P20336
RAB3A	ENST00000481914.2 linkuse as main transcript	c.285T>C	p.Ala95Ala	synonymous_variant	3/3	3		ENSP00000472335.1	M0R257
RAB3A	ENST00000464076.3 linkuse as main transcript	c.-1T>C		5_prime_UTR_variant	2/4	2		ENSP00000474603.1	S4R3Q3

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38464

AN:

151996

Hom.:

6189

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.309

AC XY:

224400

AN XY:

726922

show subpopulations

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.:

AF XY:

0.254

AC XY:

18896

AN XY:

74356

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over