chr10-16816994-T-C

Variant names:

• chr10-16816994-T-C
• rs11539866
• NM_012425.4:c.88A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012425.4(RSU1):​c.88A>G​(p.Met30Val) variant causes a missense change. The variant allele was found at a frequency of 0.00828 in 1,613,768 control chromosomes in the GnomAD database, including 752 homozygotes. 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: 𝑓 0.0096 (66 hom., cov: 33)
  • Exomes 𝑓: 0.0081 (686 hom.)
• Consequence: RSU1 NM_012425.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.05
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017714202).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSU1	NM_012425.4	MANE Select	c.88A>G	p.Met30Val	missense	Exon 2 of 9	NP_036557.1
	RSU1	NM_152724.3		c.-51+321A>G		intron	N/A	NP_689937.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSU1	ENST00000345264.10	TSL:1 MANE Select	c.88A>G	p.Met30Val	missense	Exon 2 of 9	ENSP00000339521.5
	RSU1	ENST00000377921.7	TSL:1	c.88A>G	p.Met30Val	missense	Exon 1 of 8	ENSP00000367154.3
	RSU1	ENST00000602389.1	TSL:1	c.-51+321A>G		intron	N/A	ENSP00000473588.1

Frequencies

GnomAD3 genomes AF: 0.00962 AC: 1465 AN: 152224 Hom.: 66 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0279

Gnomad FIN AF: 0.0409

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00126

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.0171 AC: 4294 AN: 251442 AF XY: 0.0172

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00367

Gnomad EAS exome AF: 0.127

Gnomad FIN exome AF: 0.0413

Gnomad NFE exome AF: 0.00154

Gnomad OTH exome AF: 0.0132

GnomAD4 exome AF: 0.00814 AC: 11896 AN: 1461426 Hom.: 686 Cov.: 30 AF XY: 0.00860 AC XY: 6255 AN XY: 727046

African (AFR) AF: 0.000179 AC: 6 AN: 33470

American (AMR) AF: 0.000559 AC: 25 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00341 AC: 89 AN: 26132

East Asian (EAS) AF: 0.162 AC: 6422 AN: 39692

South Asian (SAS) AF: 0.0241 AC: 2083 AN: 86254

European-Finnish (FIN) AF: 0.0387 AC: 2069 AN: 53418

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5768

European-Non Finnish (NFE) AF: 0.000507 AC: 564 AN: 1111592

Other (OTH) AF: 0.0103 AC: 621 AN: 60376

GnomAD4 genome AF: 0.00960 AC: 1462 AN: 152342 Hom.: 66 Cov.: 33 AF XY: 0.0125 AC XY: 928 AN XY: 74508

African (AFR) AF: 0.000216 AC: 9 AN: 41584

American (AMR) AF: 0.00222 AC: 34 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.143 AC: 742 AN: 5174

South Asian (SAS) AF: 0.0279 AC: 135 AN: 4832

European-Finnish (FIN) AF: 0.0409 AC: 435 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00126 AC: 86 AN: 68032

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00611 Hom.: 102

Bravo AF: 0.00697

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0169 AC: 2049

Asia WGS AF: 0.0580 AC: 202 AN: 3478

EpiCase AF: 0.000872

EpiControl AF: 0.000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.042
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		7.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.080
Sift	Benign	0.24	T
Sift4G	Benign	0.16	T
Polyphen		0.0010	B
Vest4		0.33
MPC		0.30
ClinPred		0.028	T
GERP RS		4.1
PromoterAI		-0.071	Neutral
Varity_R		0.22
gMVP		0.41
Mutation Taster		=96/4	polymorphism (auto)

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: rs11539866; hg19: chr10-16858993; COSMIC: COSV61709976;