10-16817077-G-A

Variant names:

• chr10-16817077-G-A
• rs546283132
• NM_012425.4:c.5C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S2C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RSU1 NM_012425.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.80
• Publications: 0 publications found

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

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

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012425.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSU1	NM_012425.4	MANE Select	c.5C>T	p.Ser2Phe	missense	Exon 2 of 9	NP_036557.1	Q15404-1
	RSU1	NM_152724.3		c.-51+238C>T		intron	N/A	NP_689937.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSU1	ENST00000345264.10	TSL:1 MANE Select	c.5C>T	p.Ser2Phe	missense	Exon 2 of 9	ENSP00000339521.5	Q15404-1
	RSU1	ENST00000377921.7	TSL:1	c.5C>T	p.Ser2Phe	missense	Exon 1 of 8	ENSP00000367154.3	Q15404-1
	RSU1	ENST00000602389.1	TSL:1	c.-51+238C>T		intron	N/A	ENSP00000473588.1	Q15404-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		8.8
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.58
MutPred		0.29		Loss of phosphorylation at S2 (P = 0.0034)
MVP		0.57
MPC		1.0
ClinPred		1.0	D
GERP RS		5.2
PromoterAI		0.031	Neutral
Varity_R		0.73
gMVP		0.59
Mutation Taster		=34/66	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

Other links and lift over

dbSNP: rs546283132; hg19: chr10-16859076;