rs1049632

chr10-16754920-C-Achr10-16754920-C-Gchr10-16754920-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_012425.4(RSU1):c.351G>T(p.Thr117=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,610,744 control chromosomes in the GnomAD database, including 68,063 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.38 (13426 hom., cov: 31)
  • Exomes 𝑓: 0.26 (54637 hom.)
• Consequence: RSU1 NM_012425.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.708

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP7: Synonymous conserved (PhyloP=0.708 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSU1	NM_012425.4	c.351G>T	p.Thr117=	synonymous_variant	5/9	ENST00000345264.10
RSU1	NM_152724.3	c.192G>T	p.Thr64=	synonymous_variant	4/8
RSU1	XM_047425617.1	c.351G>T	p.Thr117=	synonymous_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSU1	ENST00000345264.10	c.351G>T	p.Thr117=	synonymous_variant	5/9	1	NM_012425.4	P1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57219 AN: 151770 Hom.: 13372 Cov.: 31

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.373

GnomAD3 exomes AF: 0.284 AC: 71073 AN: 249912 Hom.: 11866 AF XY: 0.276 AC XY: 37230 AN XY: 135096

Gnomad AFR exome AF: 0.676

Gnomad AMR exome AF: 0.221

Gnomad ASJ exome AF: 0.251

Gnomad EAS exome AF: 0.416

Gnomad SAS exome AF: 0.225

Gnomad FIN exome AF: 0.224

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.285

GnomAD4 exome AF: 0.262 AC: 382789 AN: 1458854 Hom.: 54637 Cov.: 31 AF XY: 0.260 AC XY: 188365 AN XY: 725738

Gnomad4 AFR exome AF: 0.684

Gnomad4 AMR exome AF: 0.235

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.379

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.286

GnomAD4 genome AF: 0.378 AC: 57341 AN: 151890 Hom.: 13426 Cov.: 31 AF XY: 0.372 AC XY: 27639 AN XY: 74218

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.379

Alfa AF: 0.288 Hom.: 3941

Bravo AF: 0.400

Asia WGS AF: 0.361 AC: 1254 AN: 3478

EpiCase AF: 0.257

EpiControl AF: 0.257

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
Cadd	Benign	4.3
Dann	Benign	0.57

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: rs1049632; hg19: chr10-16796919; COSMIC: COSV61716461;