10-16816994-T-C

Variant summary

Our verdict is Benign. Variant got -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. 12/20 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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSU1	NM_012425.4	c.88A>G	p.Met30Val	missense_variant	2/9	ENST00000345264.10
RSU1	XM_047425617.1	c.88A>G	p.Met30Val	missense_variant	1/7
RSU1	NM_152724.3	c.-51+321A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSU1	ENST00000345264.10	c.88A>G	p.Met30Val	missense_variant	2/9	1	NM_012425.4	P1

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

GnomAD3 exomes AF: 0.0171 AC: 4294 AN: 251442 Hom.: 205 AF XY: 0.0172 AC XY: 2338 AN XY: 135884

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 SAS exome AF: 0.0246

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

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000559

Gnomad4 ASJ exome AF: 0.00341

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.0241

Gnomad4 FIN exome AF: 0.0387

Gnomad4 NFE exome AF: 0.000507

Gnomad4 OTH exome AF: 0.0103

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

Gnomad4 AFR AF: 0.000216

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.0279

Gnomad4 FIN AF: 0.0409

Gnomad4 NFE AF: 0.00126

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00626 Hom.: 98

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 v4.3

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;T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.042
FATHMM_MKL	Benign	0.71	D
MetaRNN	Benign	0.0018	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L
MutationTaster	Benign	0.0045	P;P
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.59	N;N
REVEL	Benign	0.080
Sift	Benign	0.24	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.0010	B;B
Vest4		0.33
MPC		0.30
ClinPred		0.028	T
GERP RS		4.1
Varity_R		0.22
gMVP		0.41

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; COSMIC: COSV61709976;