rs557328600

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005633.4(SOS1):ā€‹c.2312T>Gā€‹(p.Ile771Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I771T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

SOS1
NM_005633.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0660
Variant links:
Genes affected
SOS1 (HGNC:11187): (SOS Ras/Rac guanine nucleotide exchange factor 1) This gene encodes a protein that is a guanine nucleotide exchange factor for RAS proteins, membrane proteins that bind guanine nucleotides and participate in signal transduction pathways. GTP binding activates and GTP hydrolysis inactivates RAS proteins. The product of this gene may regulate RAS proteins by facilitating the exchange of GTP for GDP. Mutations in this gene are associated with gingival fibromatosis 1 and Noonan syndrome type 4. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.068166256).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SOS1NM_005633.4 linkuse as main transcriptc.2312T>G p.Ile771Arg missense_variant 14/23 ENST00000402219.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SOS1ENST00000402219.8 linkuse as main transcriptc.2312T>G p.Ile771Arg missense_variant 14/231 NM_005633.4 A1Q07889-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251082
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135688
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461592
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727090
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
14
DANN
Benign
0.93
DEOGEN2
Benign
0.39
T;T;T
Eigen
Benign
-0.88
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.75
.;T;T
M_CAP
Benign
0.0054
T
MetaRNN
Benign
0.068
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
L;L;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.030
N;N;N
REVEL
Benign
0.044
Sift
Benign
0.11
T;T;T
Sift4G
Benign
0.34
T;T;T
Polyphen
0.010
B;B;.
Vest4
0.32
MutPred
0.47
Gain of disorder (P = 0.0186);Gain of disorder (P = 0.0186);Gain of disorder (P = 0.0186);
MVP
0.23
MPC
1.0
ClinPred
0.059
T
GERP RS
-2.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.20
gMVP
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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.

Other links and lift over

dbSNP: rs557328600; hg19: chr2-39239345; API