10-16695157-TGGGGGG-TGGGGGGG

Variant names:

• chr10-16695157-T-TG
• rs56715139
• NM_012425.4:c.599-3dupC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_012425.4(RSU1):​c.599-3dupC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0728 in 1,144,244 control chromosomes in the GnomAD database, including 1,724 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (809 hom., cov: 17)
  • Exomes 𝑓: 0.068 (915 hom.)
• Consequence: RSU1 NM_012425.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33
• Publications: 1 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.236 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.599-3dupC		splice_region intron	N/A	NP_036557.1	Q15404-1
	RSU1	NM_152724.3		c.440-3dupC		splice_region intron	N/A	NP_689937.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSU1	ENST00000345264.10	TSL:1 MANE Select	c.599-3_599-2insC		splice_region intron	N/A	ENSP00000339521.5	Q15404-1
	RSU1	ENST00000377921.7	TSL:1	c.599-3_599-2insC		splice_region intron	N/A	ENSP00000367154.3	Q15404-1
	RSU1	ENST00000602389.1	TSL:1	c.440-3_440-2insC		splice_region intron	N/A	ENSP00000473588.1	Q15404-2

Frequencies

GnomAD3 genomes AF: 0.115 AC: 14521 AN: 126418 Hom.: 808 Cov.: 17

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0834

Gnomad ASJ AF: 0.0765

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0599

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0988

GnomAD4 exome AF: 0.0675 AC: 68724 AN: 1017760 Hom.: 915 Cov.: 21 AF XY: 0.0674 AC XY: 34104 AN XY: 506084

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0694 AC: 1706 AN: 24574

American (AMR) AF: 0.0539 AC: 1431 AN: 26530

Ashkenazi Jewish (ASJ) AF: 0.0332 AC: 579 AN: 17456

East Asian (EAS) AF: 0.104 AC: 2703 AN: 25938

South Asian (SAS) AF: 0.0882 AC: 5087 AN: 57670

European-Finnish (FIN) AF: 0.0772 AC: 2595 AN: 33632

Middle Eastern (MID) AF: 0.0361 AC: 152 AN: 4206

European-Non Finnish (NFE) AF: 0.0659 AC: 51815 AN: 786066

Other (OTH) AF: 0.0637 AC: 2656 AN: 41688

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.115 AC: 14528 AN: 126484 Hom.: 809 Cov.: 17 AF XY: 0.116 AC XY: 6967 AN XY: 60214

African (AFR) AF: 0.113 AC: 3851 AN: 34190

American (AMR) AF: 0.0837 AC: 1080 AN: 12910

Ashkenazi Jewish (ASJ) AF: 0.0765 AC: 238 AN: 3110

East Asian (EAS) AF: 0.249 AC: 1021 AN: 4108

South Asian (SAS) AF: 0.139 AC: 483 AN: 3472

European-Finnish (FIN) AF: 0.139 AC: 917 AN: 6620

Middle Eastern (MID) AF: 0.0530 AC: 14 AN: 264

European-Non Finnish (NFE) AF: 0.112 AC: 6634 AN: 59336

Other (OTH) AF: 0.0977 AC: 170 AN: 1740

Alfa AF: 0.0564 Hom.: 109

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3
Mutation Taster		=95/5	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: rs56715139; hg19: chr10-16737156; COSMIC: COSV61714109;