NM_012425.4:c.390C>G

Variant names:

• chr10-16754881-G-C
• rs1303596198
• NM_012425.4:c.390C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012425.4(RSU1):​c.390C>G​(p.Phe130Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RSU1 NM_012425.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.18

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]

ACMG classification

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 rank	MANE	Protein	UniProt
RSU1	NM_012425.4	c.390C>G	p.Phe130Leu	missense_variant	Exon 5 of 9	ENST00000345264.10	NP_036557.1
RSU1	NM_152724.3	c.231C>G	p.Phe77Leu	missense_variant	Exon 4 of 8		NP_689937.2
RSU1	XM_047425617.1	c.390C>G	p.Phe130Leu	missense_variant	Exon 4 of 7		XP_047281573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSU1	ENST00000345264.10	c.390C>G	p.Phe130Leu	missense_variant	Exon 5 of 9	1	NM_012425.4	ENSP00000339521.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;T;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.82	.;T;T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.45	N;N;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-5.1	D;D;.
REVEL	Uncertain	0.37
Sift	Uncertain	0.011	D;D;.
Sift4G	Benign	0.16	T;T;.
Polyphen		0.98	D;D;.
Vest4		0.76
MutPred		0.54		Loss of catalytic residue at F130 (P = 0.0557);Loss of catalytic residue at F130 (P = 0.0557);.;
MVP		0.58
MPC		0.39
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.72
gMVP		0.73

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

Other links and lift over

dbSNP: rs1303596198; hg19: chr10-16796880;