10-16695157-TGGGGGG-TGGGGGGGG

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_012425.4(RSU1):​c.599-4_599-3dupCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,201,784 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 17)
  • Exomes 𝑓: 0.00089 (4 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00198 AC: 254 AN: 128100 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000921

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.00932

Gnomad FIN AF: 0.00161

Gnomad MID AF: 0.00352

Gnomad NFE AF: 0.00143

Gnomad OTH AF: 0.00116

GnomAD4 exome AF: 0.000889 AC: 954 AN: 1073620 Hom.: 4 Cov.: 21 AF XY: 0.000949 AC XY: 506 AN XY: 533348

Gnomad4 AFR exome AF: 0.000783

Gnomad4 AMR exome AF: 0.000688

Gnomad4 ASJ exome AF: 0.000167

Gnomad4 EAS exome AF: 0.00274

Gnomad4 SAS exome AF: 0.00307

Gnomad4 FIN exome AF: 0.00126

Gnomad4 NFE exome AF: 0.000647

Gnomad4 OTH exome AF: 0.00146

GnomAD4 genome AF: 0.00198 AC: 254 AN: 128164 Hom.: 0 Cov.: 17 AF XY: 0.00214 AC XY: 131 AN XY: 61100

Gnomad4 AFR AF: 0.00165

Gnomad4 AMR AF: 0.000920

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0123

Gnomad4 SAS AF: 0.00939

Gnomad4 FIN AF: 0.00161

Gnomad4 NFE AF: 0.00143

Gnomad4 OTH AF: 0.00114

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;