rs757675861

Variant names:

• chr10-16695049-C-A
• rs757675861
• NM_012425.4:c.705G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-16695049-C-A
• chr10-16695049-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012425.4(RSU1):​c.705G>T​(p.Glu235Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E235E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RSU1 NM_012425.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33919394).

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.705G>T	p.Glu235Asp	missense	Exon 8 of 9	NP_036557.1	Q15404-1
	RSU1	NM_152724.3		c.546G>T	p.Glu182Asp	missense	Exon 7 of 8	NP_689937.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSU1	ENST00000345264.10	TSL:1 MANE Select	c.705G>T	p.Glu235Asp	missense	Exon 8 of 9	ENSP00000339521.5	Q15404-1
	RSU1	ENST00000377921.7	TSL:1	c.705G>T	p.Glu235Asp	missense	Exon 7 of 8	ENSP00000367154.3	Q15404-1
	RSU1	ENST00000602389.1	TSL:1	c.546G>T	p.Glu182Asp	missense	Exon 7 of 8	ENSP00000473588.1	Q15404-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461120 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726842

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

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111488

Other (OTH) AF: 0.00 AC: 0 AN: 60360

⚠️ 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.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	0.0081	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.74
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.36	N
PhyloP100		0.12
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.77	N
REVEL	Uncertain	0.31
Sift	Benign	0.94	T
Sift4G	Benign	0.70	T
Polyphen		0.0	B
Vest4		0.81
MutPred		0.30		Gain of helix (P = 0.132)
MVP		0.19
MPC		0.27
ClinPred		0.36	T
GERP RS		-2.3
Varity_R		0.12
gMVP		0.36
Mutation Taster		=62/38	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: rs757675861; hg19: chr10-16737048;