10-16695157-TGGGGGG-TGGGG

Variant names:

• chr10-16695157-TGG-T
• rs56715139
• NM_012425.4:c.599-4_599-3delCC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_012425.4(RSU1):​c.599-4_599-3delCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 1,190,774 control chromosomes in the GnomAD database, including 739 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 0.042 (346 hom., cov: 17)
  • Exomes 𝑓: 0.014 (393 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 (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSU1	NM_012425.4	c.599-4_599-3delCC		splice_region_variant, intron_variant	Intron 7 of 8	ENST00000345264.10	NP_036557.1
RSU1	NM_152724.3	c.440-4_440-3delCC		splice_region_variant, intron_variant	Intron 6 of 7		NP_689937.2
RSU1	XM_047425617.1	c.598+57380_598+57381delCC		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.599-4_599-3delCC		splice_region_variant, intron_variant	Intron 7 of 8	1	NM_012425.4	ENSP00000339521.5

Frequencies

GnomAD3 genomes AF: 0.0424 AC: 5433 AN: 128160 Hom.: 346 Cov.: 17

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.00287

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.00590

Gnomad FIN AF: 0.0151

Gnomad MID AF: 0.0106

Gnomad NFE AF: 0.00165

Gnomad OTH AF: 0.0347

GnomAD4 exome AF: 0.0137 AC: 14545 AN: 1062550 Hom.: 393 AF XY: 0.0137 AC XY: 7217 AN XY: 527592

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.0160

Gnomad4 ASJ exome AF: 0.00998

Gnomad4 EAS exome AF: 0.148

Gnomad4 SAS exome AF: 0.0153

Gnomad4 FIN exome AF: 0.0189

Gnomad4 NFE exome AF: 0.00449

Gnomad4 OTH exome AF: 0.0249

GnomAD4 genome AF: 0.0424 AC: 5443 AN: 128224 Hom.: 346 Cov.: 17 AF XY: 0.0416 AC XY: 2543 AN XY: 61130

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.0147

Gnomad4 ASJ AF: 0.00287

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.00595

Gnomad4 FIN AF: 0.0151

Gnomad4 NFE AF: 0.00165

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0137 Hom.: 109

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;