chr10-16764464-G-T

Variant names:

• chr10-16764464-G-T
• rs1251036959
• NM_012425.4:c.207C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_012425.4(RSU1):​c.207C>A​(p.Asn69Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RSU1 NM_012425.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.45
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.865

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.207C>A	p.Asn69Lys	missense	Exon 4 of 9	NP_036557.1
	RSU1	NM_152724.3		c.48C>A	p.Asn16Lys	missense	Exon 3 of 8	NP_689937.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSU1	ENST00000345264.10	TSL:1 MANE Select	c.207C>A	p.Asn69Lys	missense	Exon 4 of 9	ENSP00000339521.5
	RSU1	ENST00000377921.7	TSL:1	c.207C>A	p.Asn69Lys	missense	Exon 3 of 8	ENSP00000367154.3
	RSU1	ENST00000602389.1	TSL:1	c.48C>A	p.Asn16Lys	missense	Exon 3 of 8	ENSP00000473588.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.042	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.5	L
PhyloP100		7.4
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.032	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.52		Gain of ubiquitination at N69 (P = 0.0276)
MVP		0.66
MPC		0.96
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.88
gMVP		0.75
Mutation Taster		=11/89	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: rs1251036959; hg19: chr10-16806463;