NM_012425.4:c.277C>A

Variant names:

• chr10-16764394-G-T
• rs749961549
• NM_012425.4:c.277C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012425.4(RSU1):​c.277C>A​(p.Leu93Ile) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L93F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RSU1 NM_012425.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.41
• 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSU1	NM_012425.4	c.277C>A	p.Leu93Ile	missense_variant	Exon 4 of 9	ENST00000345264.10	NP_036557.1
RSU1	NM_152724.3	c.118C>A	p.Leu40Ile	missense_variant	Exon 3 of 8		NP_689937.2
RSU1	XM_047425617.1	c.277C>A	p.Leu93Ile	missense_variant	Exon 3 of 7		XP_047281573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSU1	ENST00000345264.10	c.277C>A	p.Leu93Ile	missense_variant	Exon 4 of 9	1	NM_012425.4	ENSP00000339521.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T;T;.
Eigen	Benign	0.15
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	.;D;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.1	M;M;.
PhyloP100		4.4
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.98	N;N;.
REVEL	Uncertain	0.32
Sift	Benign	0.047	D;D;.
Sift4G	Benign	0.11	T;T;.
Polyphen		0.32	B;B;.
Vest4		0.67
MutPred		0.49		Gain of catalytic residue at L98 (P = 0.0682);Gain of catalytic residue at L98 (P = 0.0682);.;
MVP		0.76
MPC		0.53
ClinPred		0.92	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.48
Mutation Taster		=74/26	polymorphism

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: rs749961549; hg19: chr10-16806393;