10-16695157-TGGGGGG-TG

Variant names:

• chr10-16695157-TGGGGG-T
• rs56715139
• NM_012425.4:c.599-7_599-3delCCCCC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012425.4(RSU1):​c.599-7_599-3delCCCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000065 in 1,076,448 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: not found (cov: 17)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: RSU1 NM_012425.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.599-7_599-3delCCCCC		splice_region intron	N/A	NP_036557.1	Q15404-1
	RSU1	NM_152724.3		c.440-7_440-3delCCCCC		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.599-7_599-3delCCCCC		splice_region intron	N/A	ENSP00000339521.5	Q15404-1
	RSU1	ENST00000377921.7	TSL:1	c.599-7_599-3delCCCCC		splice_region intron	N/A	ENSP00000367154.3	Q15404-1
	RSU1	ENST00000602389.1	TSL:1	c.440-7_440-3delCCCCC		splice_region intron	N/A	ENSP00000473588.1	Q15404-2

Frequencies

GnomAD3 genomes Cov.: 17

GnomAD4 exome AF: 0.00000650 AC: 7 AN: 1076448 Hom.: 0 AF XY: 0.00000561 AC XY: 3 AN XY: 534766

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

African (AFR) AF: 0.0000391 AC: 1 AN: 25574

American (AMR) AF: 0.000108 AC: 3 AN: 27684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17980

East Asian (EAS) AF: 0.00 AC: 0 AN: 28672

South Asian (SAS) AF: 0.0000328 AC: 2 AN: 60920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4334

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 831504

Other (OTH) AF: 0.0000228 AC: 1 AN: 43918

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000000444089), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 17

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56715139; hg19: chr10-16737156;