NM_012425.4:c.599-3delC

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6 BS2

The NM_012425.4(RSU1):​c.599-3delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0086 in 1,171,714 control chromosomes in the GnomAD database, including 4 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 17)
  • Exomes 𝑓: 0.0096 (4 hom.)
• Consequence: RSU1 NM_012425.4 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: 2.33
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• BP6: Variant 10-16695157-TG-T is Benign according to our data. Variant chr10-16695157-TG-T is described in ClinVar as [Likely_benign]. Clinvar id is 1328202.Status of the report is no_assertion_criteria_provided, 0 stars.
• 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.599-3delC		splice_region_variant, intron_variant	Intron 7 of 8	ENST00000345264.10	NP_036557.1
RSU1	NM_152724.3	c.440-3delC		splice_region_variant, intron_variant	Intron 6 of 7		NP_689937.2
RSU1	XM_047425617.1	c.598+57381delC		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.599-3delC		splice_region_variant, intron_variant	Intron 7 of 8	1	NM_012425.4	ENSP00000339521.5

Frequencies

GnomAD3 genomes AF: 0.000195 AC: 25 AN: 128178 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.000232

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000154

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000281

Gnomad FIN AF: 0.000293

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000183

Gnomad OTH AF: 0.000578

GnomAD4 exome AF: 0.00964 AC: 10055 AN: 1043536 Hom.: 4 Cov.: 21 AF XY: 0.00977 AC XY: 5064 AN XY: 518274

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

African (AFR) AF: 0.00281 AC: 71 AN: 25286

American (AMR) AF: 0.0148 AC: 396 AN: 26798

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 206 AN: 17480

East Asian (EAS) AF: 0.00519 AC: 146 AN: 28152

South Asian (SAS) AF: 0.00902 AC: 534 AN: 59194

European-Finnish (FIN) AF: 0.0137 AC: 477 AN: 34784

Middle Eastern (MID) AF: 0.0120 AC: 51 AN: 4250

European-Non Finnish (NFE) AF: 0.00958 AC: 7708 AN: 804934

Other (OTH) AF: 0.0109 AC: 466 AN: 42658

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000195 AC: 25 AN: 128178 Hom.: 0 Cov.: 17 AF XY: 0.000213 AC XY: 13 AN XY: 61060

African (AFR) AF: 0.000232 AC: 8 AN: 34536

American (AMR) AF: 0.000154 AC: 2 AN: 13024

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3140

East Asian (EAS) AF: 0.00 AC: 0 AN: 4274

South Asian (SAS) AF: 0.000281 AC: 1 AN: 3558

European-Finnish (FIN) AF: 0.000293 AC: 2 AN: 6822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.000183 AC: 11 AN: 60070

Other (OTH) AF: 0.000578 AC: 1 AN: 1730

Alfa AF: 0.0165 Hom.: 109

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

not provided Benign:2

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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

dbSNP: rs56715139; hg19: chr10-16737156; COSMIC: COSV61708791;