10-16764546-A-G

Variant names:

• chr10-16764546-A-G
• rs3765595
• NM_012425.4:c.161-36T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012425.4(RSU1):​c.161-36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RSU1 NM_012425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSU1	NM_012425.4	c.161-36T>C		intron_variant	Intron 3 of 8	ENST00000345264.10	NP_036557.1
RSU1	NM_152724.3	c.2-36T>C		intron_variant	Intron 2 of 7		NP_689937.2
RSU1	XM_047425617.1	c.161-36T>C		intron_variant	Intron 2 of 6		XP_047281573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSU1	ENST00000345264.10	c.161-36T>C		intron_variant	Intron 3 of 8	1	NM_012425.4	ENSP00000339521.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444202 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 716834

African (AFR) AF: 0.00 AC: 0 AN: 32868

American (AMR) AF: 0.00 AC: 0 AN: 42948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25730

East Asian (EAS) AF: 0.00 AC: 0 AN: 39134

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83628

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101374

Other (OTH) AF: 0.00 AC: 0 AN: 59688

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.25
DANN	Benign	0.30
PhyloP100		0.17

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: rs3765595; hg19: chr10-16806545;