Variant 19-18202721-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002866.5(RAB3A):c.20C>G(p.Ser7Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RAB3A
NM_002866.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.48

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:

RAB3A (HGNC:):

RAB3A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37782705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB3A	NM_002866.5 linkuse as main transcript	c.20C>G	p.Ser7Trp	missense_variant	2/5	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.20C>G	p.Ser7Trp	missense_variant	2/5	1	NM_002866.5	ENSP00000222256.3	P20336
RAB3A	ENST00000481914.2 linkuse as main transcript	c.20C>G	p.Ser7Trp	missense_variant	2/3	3		ENSP00000472335.1	M0R257
RAB3A	ENST00000464076.3 linkuse as main transcript	c.-58+1175C>G		intron_variant		2		ENSP00000474603.1	S4R3Q3
RAB3A	ENST00000515410.1 linkuse as main transcript	n.160C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 03, 2022

The c.20C>G (p.S7W) alteration is located in exon 2 (coding exon 1) of the RAB3A gene. This alteration results from a C to G substitution at nucleotide position 20, causing the serine (S) at amino acid position 7 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.45

T;T

Eigen

Benign

0.018

Eigen_PC

Benign

0.025

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.93

D;D

M_CAP

Uncertain

0.094

MetaRNN

Benign

0.38

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.1

L;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.4

N;.

REVEL

Benign

0.26

Sift

Uncertain

0.0030

D;.

Sift4G

Uncertain

0.0060

D;.

Polyphen

0.84

P;.

Vest4

0.47

MutPred

0.47

Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);

MVP

0.71

MPC

1.7

ClinPred

0.90

GERP RS

3.3

Varity_R

0.12

gMVP

0.65

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over