rs546283132

Variant names:

• chr10-16817077-G-A
• NM_012425.4:c.5C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-16817077-G-A
• chr10-16817077-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_012425.4(RSU1):​c.5C>T​(p.Ser2Phe) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 33)
• Consequence: RSU1 NM_012425.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.80

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 4 ACMG points.

• PM1: In a modified_residue N-acetylserine (size 0) in uniprot entity RSU1_HUMAN
• 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.5C>T	p.Ser2Phe	missense_variant	Exon 2 of 9	ENST00000345264.10	NP_036557.1
RSU1	XM_047425617.1	c.5C>T	p.Ser2Phe	missense_variant	Exon 1 of 7		XP_047281573.1
RSU1	NM_152724.3	c.-51+238C>T		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	c.5C>T	p.Ser2Phe	missense_variant	Exon 2 of 9	1	NM_012425.4	ENSP00000339521.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.92	.;D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.4	D;D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.99	D;D
Vest4		0.58
MutPred		0.29		Loss of phosphorylation at S2 (P = 0.0034);Loss of phosphorylation at S2 (P = 0.0034);
MVP		0.57
MPC		1.0
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.73
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-16859076;