Variant 13-113999606-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_007368.4(RASA3):c.1911G>A(p.Glu637Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,613,234 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 27)

Exomes 𝑓: 0.0022 ( 6 hom. )

Consequence

RASA3
NM_007368.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.625

Variant links:

Genes affected

RASA3 (HGNC:20331): (RAS p21 protein activator 3) This gene encodes a protein that binds inositol 1,3,4,5-tetrakisphosphate and stimulates the GTPase activity of Ras p21. This protein functions as a negative regulator of the Ras signalling pathway. It is localized to the cell membrane via a pleckstrin homology (PH) domain in the C-terminal region. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

RASA3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 13-113999606-C-T is Benign according to our data. Variant chr13-113999606-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2644017.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.625 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASA3	NM_007368.4 linkuse as main transcript	c.1911G>A	p.Glu637Glu	synonymous_variant	20/24	ENST00000334062.8	NP_031394.2	Q14644-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASA3	ENST00000334062.8 linkuse as main transcript	c.1911G>A	p.Glu637Glu	synonymous_variant	20/24	1	NM_007368.4	ENSP00000335029.7		Q14644-1

Frequencies

GnomAD3 genomes

AF:

0.00192

AC:

291

AN:

151374

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000316

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00434

Gnomad ASJ

AF:

0.00376

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00262

Gnomad OTH

AF:

0.00337

GnomAD3 exomes

AF:

0.00182

AC:

456

AN:

250762

Hom.:

AF XY:

0.00177

AC XY:

240

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.00330

Gnomad ASJ exome

AF:

0.00358

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00241

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00216

AC:

3156

AN:

1461742

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

1624

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.00380

Gnomad4 ASJ exome

AF:

0.00409

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000290

Gnomad4 FIN exome

AF:

0.000281

Gnomad4 NFE exome

AF:

0.00242

Gnomad4 OTH exome

AF:

0.00215

GnomAD4 genome

AF:

0.00192

AC:

291

AN:

151492

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

140

AN XY:

74016

show subpopulations

Gnomad4 AFR

AF:

0.000315

Gnomad4 AMR

AF:

0.00433

Gnomad4 ASJ

AF:

0.00376

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.00262

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.00200

Hom.:

Bravo

AF:

0.00224

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00382

EpiControl

AF:

0.00296

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

RASA3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.2

DANN

Benign

0.43

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