10-16752565-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012425.4(RSU1):​c.572G>A​(p.Arg191His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,956 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R191C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

RSU1
NM_012425.4 missense

Scores

7
5
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.54

Publications

6 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RSU1NM_012425.4 linkc.572G>A p.Arg191His missense_variant Exon 7 of 9 ENST00000345264.10 NP_036557.1 Q15404-1
RSU1NM_152724.3 linkc.413G>A p.Arg138His missense_variant Exon 6 of 8 NP_689937.2 Q15404-2
RSU1XM_047425617.1 linkc.572G>A p.Arg191His missense_variant Exon 6 of 7 XP_047281573.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RSU1ENST00000345264.10 linkc.572G>A p.Arg191His missense_variant Exon 7 of 9 1 NM_012425.4 ENSP00000339521.5 Q15404-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152142
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000159
AC:
4
AN:
251350
AF XY:
0.0000221
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461696
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
727170
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33480
American (AMR)
AF:
0.0000224
AC:
1
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86252
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53404
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000899
AC:
10
AN:
1111840
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.457
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00000657
AC:
1
AN:
152260
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74450
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41568
American (AMR)
AF:
0.00
AC:
0
AN:
15298
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5182
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10594
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68006
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.0000202
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.79
BayesDel_addAF
Benign
-0.013
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.18
T;T;.
Eigen
Pathogenic
0.69
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
.;D;D
M_CAP
Benign
0.036
D
MetaRNN
Uncertain
0.64
D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.15
N;N;.
PhyloP100
7.5
PrimateAI
Pathogenic
0.86
D
PROVEAN
Uncertain
-4.3
D;D;.
REVEL
Uncertain
0.42
Sift
Uncertain
0.0040
D;D;.
Sift4G
Uncertain
0.020
D;D;.
Polyphen
1.0
D;D;.
Vest4
0.68
MutPred
0.36
Gain of catalytic residue at N190 (P = 0.1784);Gain of catalytic residue at N190 (P = 0.1784);.;
MVP
0.41
MPC
0.70
ClinPred
0.82
D
GERP RS
5.3
Varity_R
0.44
gMVP
0.70
Mutation Taster
=25/75
disease causing

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

Other links and lift over

dbSNP: rs200600927; hg19: chr10-16794564; COSMIC: COSV61710188; COSMIC: COSV61710188; API