rs113149562

Variant names:

• chr17-80837970-G-A
• rs113149562
• NM_020761.3:c.1185G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-80837970-G-A
• chr17-80837970-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_020761.3(RPTOR):​c.1185G>A​(p.Thr395Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00447 in 1,611,670 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (38 hom., cov: 33)
  • Exomes 𝑓: 0.0035 (65 hom.)
• Consequence: RPTOR NM_020761.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.707
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 17-80837970-G-A is Benign according to our data. Variant chr17-80837970-G-A is described in ClinVar as Benign. ClinVar VariationId is 778753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.707 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0141 (2143/152286) while in subpopulation AFR AF = 0.04 (1664/41556). AF 95% confidence interval is 0.0384. There are 38 homozygotes in GnomAd4. There are 990 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2143 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	NM_020761.3	MANE Select	c.1185G>A	p.Thr395Thr	synonymous	Exon 10 of 34	NP_065812.1	Q8N122-1
	RPTOR	NM_001163034.2		c.1185G>A	p.Thr395Thr	synonymous	Exon 10 of 30	NP_001156506.1	Q8N122-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	ENST00000306801.8	TSL:1 MANE Select	c.1185G>A	p.Thr395Thr	synonymous	Exon 10 of 34	ENSP00000307272.3	Q8N122-1
	RPTOR	ENST00000575542.5	TSL:1	n.672G>A		non_coding_transcript_exon	Exon 6 of 30
	RPTOR	ENST00000697423.1		c.1239G>A	p.Thr413Thr	synonymous	Exon 10 of 34	ENSP00000513305.1	A0A8V8TMD9

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2132 AN: 152168 Hom.: 36 Cov.: 33

Gnomad AFR AF: 0.0399

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00243

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.00563 AC: 1391 AN: 246888 AF XY: 0.00474

Gnomad AFR exome AF: 0.0422

Gnomad AMR exome AF: 0.00905

Gnomad ASJ exome AF: 0.00718

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.0000471

Gnomad NFE exome AF: 0.00257

Gnomad OTH exome AF: 0.0104

GnomAD4 exome AF: 0.00347 AC: 5057 AN: 1459384 Hom.: 65 Cov.: 31 AF XY: 0.00328 AC XY: 2381 AN XY: 725700

African (AFR) AF: 0.0430 AC: 1438 AN: 33454

American (AMR) AF: 0.0103 AC: 459 AN: 44532

Ashkenazi Jewish (ASJ) AF: 0.00781 AC: 203 AN: 25984

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000701 AC: 6 AN: 85554

European-Finnish (FIN) AF: 0.0000376 AC: 2 AN: 53152

Middle Eastern (MID) AF: 0.0130 AC: 75 AN: 5766

European-Non Finnish (NFE) AF: 0.00217 AC: 2416 AN: 1110938

Other (OTH) AF: 0.00759 AC: 458 AN: 60316

GnomAD4 genome AF: 0.0141 AC: 2143 AN: 152286 Hom.: 38 Cov.: 33 AF XY: 0.0133 AC XY: 990 AN XY: 74458

African (AFR) AF: 0.0400 AC: 1664 AN: 41556

American (AMR) AF: 0.0160 AC: 245 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00691 AC: 24 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.00243 AC: 165 AN: 68024

Other (OTH) AF: 0.0151 AC: 32 AN: 2114

Alfa AF: 0.00688 Hom.: 9

Bravo AF: 0.0168

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.3
DANN	Benign	0.77
PhyloP100		-0.71
Mutation Taster		=100/0	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: rs113149562; hg19: chr17-78811770; COSMIC: COSV100157812;