chr10-16754920-C-A

Variant names:

• chr10-16754920-C-A
• rs1049632
• NM_012425.4:c.351G>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_012425.4(RSU1):​c.351G>T​(p.Thr117Thr) 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
• Publications: 16 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 -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.

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.351G>T	p.Thr117Thr	synonymous	Exon 5 of 9	NP_036557.1	Q15404-1
	RSU1	NM_152724.3		c.192G>T	p.Thr64Thr	synonymous	Exon 4 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.351G>T	p.Thr117Thr	synonymous	Exon 5 of 9	ENSP00000339521.5	Q15404-1
	RSU1	ENST00000377921.7	TSL:1	c.351G>T	p.Thr117Thr	synonymous	Exon 4 of 8	ENSP00000367154.3	Q15404-1
	RSU1	ENST00000602389.1	TSL:1	c.192G>T	p.Thr64Thr	synonymous	Exon 4 of 8	ENSP00000473588.1	Q15404-2

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

GnomAD2 exomes AF: 0.284 AC: 71073 AN: 249912 AF XY: 0.276

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 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

African (AFR) AF: 0.684 AC: 22761 AN: 33296

American (AMR) AF: 0.235 AC: 10469 AN: 44536

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 6506 AN: 26060

East Asian (EAS) AF: 0.379 AC: 14985 AN: 39524

South Asian (SAS) AF: 0.225 AC: 19306 AN: 85926

European-Finnish (FIN) AF: 0.224 AC: 11963 AN: 53362

Middle Eastern (MID) AF: 0.300 AC: 1720 AN: 5736

European-Non Finnish (NFE) AF: 0.250 AC: 277872 AN: 1110168

Other (OTH) AF: 0.286 AC: 17207 AN: 60246

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

African (AFR) AF: 0.671 AC: 27786 AN: 41396

American (AMR) AF: 0.329 AC: 5020 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 890 AN: 3468

East Asian (EAS) AF: 0.394 AC: 2022 AN: 5138

South Asian (SAS) AF: 0.229 AC: 1102 AN: 4814

European-Finnish (FIN) AF: 0.226 AC: 2386 AN: 10546

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 17019 AN: 67960

Other (OTH) AF: 0.379 AC: 797 AN: 2104

Alfa AF: 0.296 Hom.: 5423

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	4.3
DANN	Benign	0.57
PhyloP100		0.71
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: rs1049632; hg19: chr10-16796919; COSMIC: COSV61716461;