Genetic Variant RSU1:c.599-5_599-3delCCC (chr10-16695157-TGGG-T) – 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.599-5_599-3delCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000996 in 1,204,618 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000023 ( 0 hom., cov: 17)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

RSU1
NM_012425.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.45

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

Frequencies

GnomAD3 genomes

AF:

0.0000234

AC:

AN:

128198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000869

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000836

AC:

AN:

1076354

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

534716

show subpopulations

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

African (AFR)

AF:

0.0000782

AC:

AN:

25570

American (AMR)

AF:

0.0000361

AC:

AN:

27684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17978

East Asian (EAS)

AF:

0.0000349

AC:

AN:

28666

South Asian (SAS)

AF:

0.0000328

AC:

AN:

60914

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35862

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4334

European-Non Finnish (NFE)

AF:

0.00000241

AC:

AN:

831430

Other (OTH)

AF:

0.0000228

AC:

AN:

43916

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000238487), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

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:

0.0000234

AC:

AN:

128264

Hom.:

Cov.:

AF XY:

0.0000327

AC XY:

AN XY:

61140

show subpopulations

African (AFR)

AF:

0.0000866

AC:

AN:

34630

American (AMR)

AF:

0.00

AC:

AN:

13052

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3140

East Asian (EAS)

AF:

0.00

AC:

AN:

4256

South Asian (SAS)

AF:

0.00

AC:

AN:

3532

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6826

Middle Eastern (MID)

AF:

0.00

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

60074

Other (OTH)

AF:

0.00

AC:

AN:

1750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.4

Mutation Taster

=90/10

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

10-16695157-TGGGGGG-TGGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over