rs11539866

chr10-16816994-T-Achr10-16816994-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012425.4(RSU1):c.88A>T(p.Met30Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RSU1 NM_012425.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.05

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1754795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSU1	NM_012425.4	c.88A>T	p.Met30Leu	missense_variant	2/9	ENST00000345264.10
RSU1	XM_047425617.1	c.88A>T	p.Met30Leu	missense_variant	1/7
RSU1	NM_152724.3	c.-51+321A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSU1	ENST00000345264.10	c.88A>T	p.Met30Leu	missense_variant	2/9	1	NM_012425.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	21
Dann	Benign	0.94
DEOGEN2	Benign	0.015	T;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.73	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.40	N;N
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.52	N;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.49
MutPred		0.46		Loss of disorder (P = 0.1253);Loss of disorder (P = 0.1253);
MVP		0.31
MPC		0.27
ClinPred		0.33	T
GERP RS		4.1
Varity_R		0.24
gMVP		0.31

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: rs11539866; hg19: chr10-16858993;