Genetic Variant RSU1:c.599-8_599-3dupCCCCCC (chr10-16695157-T-TGGGGGG) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_012425.4(RSU1):c.599-8_599-3dupCCCCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000581 in 1,204,630 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 0.000031 ( 0 hom., cov: 17)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

RSU1
NM_012425.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.33

Publications

1 publications found

Variant links:

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]

RSU1 links:

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ACMG classification

Classification was made for transcript

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.599-8_599-3dupCCCCCC		splice_region intron	N/A	NP_036557.1	Q15404-1
	RSU1	NM_152724.3		c.440-8_440-3dupCCCCCC		splice_region intron	N/A	NP_689937.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RSU1	ENST00000345264.10	TSL:1 MANE Select	c.599-3_599-2insCCCCCC	splice_region intron	N/A	ENSP00000339521.5	Q15404-1
RSU1	ENST00000377921.7	TSL:1	c.599-3_599-2insCCCCCC	splice_region intron	N/A	ENSP00000367154.3	Q15404-1
RSU1	ENST00000602389.1	TSL:1	c.440-3_440-2insCCCCCC	splice_region intron	N/A	ENSP00000473588.1	Q15404-2

Frequencies

GnomAD3 genomes

AF:

0.0000312

AC:

AN:

128196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000333

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000279

AC:

AN:

1076434

Hom.:

Cov.:

AF XY:

0.00000187

AC XY:

AN XY:

534758

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

25580

American (AMR)

AF:

0.00

AC:

AN:

27682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17980

East Asian (EAS)

AF:

0.00

AC:

AN:

28672

South Asian (SAS)

AF:

0.00

AC:

AN:

60920

European-Finnish (FIN)

AF:

0.0000558

AC:

AN:

35862

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4334

European-Non Finnish (NFE)

AF:

0.00000120

AC:

AN:

831488

Other (OTH)

AF:

0.00

AC:

AN:

43916

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.258

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000312

AC:

AN:

128196

Hom.:

Cov.:

AF XY:

0.0000164

AC XY:

AN XY:

61072

show subpopulations

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

African (AFR)

AF:

0.0000579

AC:

AN:

34536

American (AMR)

AF:

0.00

AC:

AN:

13028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3140

East Asian (EAS)

AF:

0.00

AC:

AN:

4274

South Asian (SAS)

AF:

0.00

AC:

AN:

3558

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6828

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0000333

AC:

AN:

60078

Other (OTH)

AF:

0.00

AC:

AN:

1730

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

109

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.3

Mutation Taster

=83/17

polymorphism

(source)

Splicing

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

Publications

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10-16695157-TGGGGGG-TGGGGGGGGGGGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over