17-80625855-G-A

Variant names:

• chr17-80625855-G-A
• rs901065
• NM_020761.3:c.265+62G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_020761.3(RPTOR):​c.265+62G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000573 in 1,046,648 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: 0.0000057 (0 hom.)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 8 publications found

Genes affected

RPTOR (HGNC:30287): (regulatory associated protein of MTOR complex 1) This gene encodes a component of a signaling pathway that regulates cell growth in response to nutrient and insulin levels. The encoded protein forms a stoichiometric complex with the mTOR kinase, and also associates with eukaryotic initiation factor 4E-binding protein-1 and ribosomal protein S6 kinase. The protein positively regulates the downstream effector ribosomal protein S6 kinase, and negatively regulates the mTOR kinase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020761.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	NM_020761.3	MANE Select	c.265+62G>A		intron	N/A	NP_065812.1
	RPTOR	NM_001163034.2		c.265+62G>A		intron	N/A	NP_001156506.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	ENST00000306801.8	TSL:1 MANE Select	c.265+62G>A		intron	N/A	ENSP00000307272.3
	RPTOR	ENST00000570891.5	TSL:1	c.265+62G>A		intron	N/A	ENSP00000460136.1
	RPTOR	ENST00000697423.1		c.319+62G>A		intron	N/A	ENSP00000513305.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000573 AC: 6 AN: 1046648 Hom.: 0 AF XY: 0.00000743 AC XY: 4 AN XY: 538624

African (AFR) AF: 0.00 AC: 0 AN: 25824

American (AMR) AF: 0.00 AC: 0 AN: 43804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23326

East Asian (EAS) AF: 0.00 AC: 0 AN: 37962

South Asian (SAS) AF: 0.00 AC: 0 AN: 77740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3358

European-Non Finnish (NFE) AF: 0.00000680 AC: 5 AN: 735502

Other (OTH) AF: 0.0000215 AC: 1 AN: 46522

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 3533

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.80
PhyloP100		0.058

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: rs901065; hg19: chr17-78599655;