Genetic Variant NM_012425.4:c.599-7_599-3dupCCCCC (chr10-16695157-T-TGGGGG) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_012425.4(RSU1):c.599-7_599-3dupCCCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000216 in 1,204,566 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 0.000094 ( 0 hom., cov: 17)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

RSU1
NM_012425.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.33

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RSU1	NM_012425.4 link	c.599-7_599-3dupCCCCC	splice_region_variant, intron_variant	Intron 7 of 8	ENST00000345264.10	NP_036557.1	Q15404-1
RSU1	NM_152724.3 link	c.440-7_440-3dupCCCCC	splice_region_variant, intron_variant	Intron 6 of 7		NP_689937.2	Q15404-2
RSU1	XM_047425617.1 link	c.598+57377_598+57381dupCCCCC	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 link	c.599-3_599-2insCCCCC		splice_region_variant, intron_variant	Intron 7 of 8	1	NM_012425.4	ENSP00000339521.5		Q15404-1

Frequencies

GnomAD3 genomes

AF:

0.0000936

AC:

AN:

128170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000869

Gnomad AMI

AF:

0.00136

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000281

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000999

Gnomad OTH

AF:

0.000578

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1076330

Hom.:

Cov.:

AF XY:

0.0000150

AC XY:

AN XY:

534718

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000556

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000164

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000936

AC:

AN:

128236

Hom.:

Cov.:

AF XY:

0.0000654

AC XY:

AN XY:

61126

show subpopulations

Gnomad4 AFR

AF:

0.0000867

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000283

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000999

Gnomad4 OTH

AF:

0.000571

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over