chr10-16695157-T-TGGG

Variant names:

• chr10-16695157-T-TGGG
• rs56715139
• NM_012425.4:c.599-5_599-3dupCCC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012425.4(RSU1):​c.599-5_599-3dupCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000847 in 1,204,084 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 17)
  • Exomes 𝑓: 0.000085 (0 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSU1	NM_012425.4	c.599-5_599-3dupCCC		splice_region_variant, intron_variant	Intron 7 of 8	ENST00000345264.10	NP_036557.1
RSU1	NM_152724.3	c.440-5_440-3dupCCC		splice_region_variant, intron_variant	Intron 6 of 7		NP_689937.2
RSU1	XM_047425617.1	c.598+57379_598+57381dupCCC		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_599-2insCCC		splice_region_variant, intron_variant	Intron 7 of 8	1	NM_012425.4	ENSP00000339521.5

Frequencies

GnomAD3 genomes AF: 0.0000858 AC: 11 AN: 128176 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000767

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000234

Gnomad SAS AF: 0.000843

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000999

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000846 AC: 91 AN: 1075842 Hom.: 0 Cov.: 21 AF XY: 0.0000805 AC XY: 43 AN XY: 534452

Gnomad4 AFR exome AF: 0.0000391

Gnomad4 AMR exome AF: 0.0000723

Gnomad4 ASJ exome AF: 0.0000556

Gnomad4 EAS exome AF: 0.0000349

Gnomad4 SAS exome AF: 0.0000986

Gnomad4 FIN exome AF: 0.000223

Gnomad4 NFE exome AF: 0.0000830

Gnomad4 OTH exome AF: 0.0000683

GnomAD4 genome AF: 0.0000858 AC: 11 AN: 128242 Hom.: 0 Cov.: 17 AF XY: 0.000131 AC XY: 8 AN XY: 61128

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000766

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000235

Gnomad4 SAS AF: 0.000849

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000999

Gnomad4 OTH AF: 0.00

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;