Genetic Variant RSU1:p.Met30Val (chr10-16816994-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012425.4(RSU1):c.88A>G(p.Met30Val) variant causes a missense change. The variant allele was found at a frequency of 0.00828 in 1,613,768 control chromosomes in the GnomAD database, including 752 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0096 ( 66 hom., cov: 33)

Exomes 𝑓: 0.0081 ( 686 hom. )

Consequence

RSU1
NM_012425.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.05

Publications

10 publications found

Variant links:

Genes affected

RSU1 (HGNC:10464): (Ras suppressor protein 1) This gene encodes a protein that is involved in the Ras signal transduction pathway, growth inhibition, and nerve-growth factor induced differentiation processes, as determined in mouse and human cell line studies. In mouse, the encoded protein was initially isolated based on its ability to inhibit v-Ras transformation. Multiple alternatively spliced transcript variants for this gene have been reported; one of these variants was found only in glioma tumors. [provided by RefSeq, Jul 2008]

RSU1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017714202).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
RSU1	NM_012425.4 link	c.88A>G	p.Met30Val	missense_variant	Exon 2 of 9	ENST00000345264.10	NP_036557.1
RSU1	XM_047425617.1 link	c.88A>G	p.Met30Val	missense_variant	Exon 1 of 7		XP_047281573.1
RSU1	NM_152724.3 link	c.-51+321A>G		intron_variant	Intron 1 of 7		NP_689937.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSU1	ENST00000345264.10 link	c.88A>G	p.Met30Val	missense_variant	Exon 2 of 9	1	NM_012425.4	ENSP00000339521.5

Frequencies

GnomAD3 genomes

AF:

0.00962

AC:

1465

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.0279

Gnomad FIN

AF:

0.0409

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00126

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.0171

AC:

4294

AN:

251442

AF XY:

0.0172

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00367

Gnomad EAS exome

AF:

0.127

Gnomad FIN exome

AF:

0.0413

Gnomad NFE exome

AF:

0.00154

Gnomad OTH exome

AF:

0.0132

GnomAD4 exome

AF:

0.00814

AC:

11896

AN:

1461426

Hom.:

686

Cov.:

AF XY:

0.00860

AC XY:

6255

AN XY:

727046

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33470

American (AMR)

AF:

0.000559

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00341

AC:

AN:

26132

East Asian (EAS)

AF:

0.162

AC:

6422

AN:

39692

South Asian (SAS)

AF:

0.0241

AC:

2083

AN:

86254

European-Finnish (FIN)

AF:

0.0387

AC:

2069

AN:

53418

Middle Eastern (MID)

AF:

0.00295

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000507

AC:

564

AN:

1111592

Other (OTH)

AF:

0.0103

AC:

621

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

606

1212

1818

2424

3030

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

256

384

512

640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00960

AC:

1462

AN:

152342

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

928

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.000216

AC:

AN:

41584

American (AMR)

AF:

0.00222

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3472

East Asian (EAS)

AF:

0.143

AC:

742

AN:

5174

South Asian (SAS)

AF:

0.0279

AC:

135

AN:

4832

European-Finnish (FIN)

AF:

0.0409

AC:

435

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00126

AC:

AN:

68032

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

132

198

264

330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00611

Hom.:

102

Bravo

AF:

0.00697

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0169

AC:

2049

Asia WGS

AF:

0.0580

AC:

202

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

-0.11

Eigen_PC

Benign

0.042

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.90

.;D

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L

PhyloP100

7.0

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.59

N;N

REVEL

Benign

0.080

Sift

Benign

0.24

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.0010

B;B

Vest4

0.33

MPC

0.30

ClinPred

0.028

GERP RS

4.1

PromoterAI

-0.071

Neutral

(source)

Varity_R

0.22

gMVP

0.41

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over