10-16752565-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_012425.4(RSU1):c.572G>T(p.Arg191Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,613,956 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000053 ( 0 hom. )
Consequence
RSU1
NM_012425.4 missense
NM_012425.4 missense
Scores
4
8
7
Clinical Significance
Conservation
PhyloP100: 7.54
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RSU1 | NM_012425.4 | c.572G>T | p.Arg191Leu | missense_variant | 7/9 | ENST00000345264.10 | NP_036557.1 | |
RSU1 | NM_152724.3 | c.413G>T | p.Arg138Leu | missense_variant | 6/8 | NP_689937.2 | ||
RSU1 | XM_047425617.1 | c.572G>T | p.Arg191Leu | missense_variant | 6/7 | XP_047281573.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RSU1 | ENST00000345264.10 | c.572G>T | p.Arg191Leu | missense_variant | 7/9 | 1 | NM_012425.4 | ENSP00000339521.5 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251350Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135844
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GnomAD4 exome AF: 0.0000534 AC: 78AN: 1461696Hom.: 0 Cov.: 30 AF XY: 0.0000509 AC XY: 37AN XY: 727170
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152260Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74450
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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 | Apr 20, 2024 | The c.572G>T (p.R191L) alteration is located in exon 7 (coding exon 6) of the RSU1 gene. This alteration results from a G to T substitution at nucleotide position 572, causing the arginine (R) at amino acid position 191 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;.
REVEL
Uncertain
Sift
Uncertain
D;D;.
Sift4G
Benign
T;T;.
Polyphen
P;P;.
Vest4
MutPred
Loss of solvent accessibility (P = 0.0606);Loss of solvent accessibility (P = 0.0606);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at