NM_012425.4:c.599-3dupC

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSU1	NM_012425.4	c.599-3dupC		splice_region_variant, intron_variant	Intron 7 of 8	ENST00000345264.10	NP_036557.1
RSU1	NM_152724.3	c.440-3dupC		splice_region_variant, intron_variant	Intron 6 of 7		NP_689937.2
RSU1	XM_047425617.1	c.598+57381dupC		intron_variant	Intron 6 of 6		XP_047281573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSU1	ENST00000345264.10	c.599-3_599-2insC		splice_region_variant, intron_variant	Intron 7 of 8	1	NM_012425.4	ENSP00000339521.5

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

Gnomad4 AFR exome AF: 0.0694

Gnomad4 AMR exome AF: 0.0539

Gnomad4 ASJ exome AF: 0.0332

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.0882

Gnomad4 FIN exome AF: 0.0772

Gnomad4 NFE exome AF: 0.0659

Gnomad4 OTH exome AF: 0.0637

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

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0837

Gnomad4 ASJ AF: 0.0765

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.0977

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs56715139; hg19: chr10-16737156;