Variant chr5-38950299-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_152756.5(RICTOR):c.3549A>C(p.Leu1183Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,613,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

RICTOR
NM_152756.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0100

Variant links:

Genes affected

RICTOR (HGNC:28611): (RPTOR independent companion of MTOR complex 2) RICTOR and MTOR (FRAP1; MIM 601231) are components of a protein complex that integrates nutrient- and growth factor-derived signals to regulate cell growth (Sarbassov et al., 2004 [PubMed 15268862]).[supplied by OMIM, Mar 2008]

RICTOR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.036473066).

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RICTOR	NM_152756.5 linkuse as main transcript	c.3549A>C	p.Leu1183Phe	missense_variant	31/38	ENST00000357387.8	NP_689969.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RICTOR	ENST00000357387.8 linkuse as main transcript	c.3549A>C	p.Leu1183Phe	missense_variant	31/38	1	NM_152756.5	ENSP00000349959	P4	Q6R327-1

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000591

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000598

AC:

AN:

250770

Hom.:

AF XY:

0.0000738

AC XY:

AN XY:

135544

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000442

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.0000390

AC:

AN:

1461438

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

727034

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000306

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000658

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000591

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2023

The c.3549A>C (p.L1183F) alteration is located in exon 31 (coding exon 31) of the RICTOR gene. This alteration results from a A to C substitution at nucleotide position 3549, causing the leucine (L) at amino acid position 1183 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.059

T;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.036

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.59

N;N

REVEL

Benign

0.084

Sift

Benign

0.28

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.0020

B;B

Vest4

0.34

MutPred

0.20

Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);

MVP

0.11

MPC

0.44

ClinPred

0.020

GERP RS

-1.3

Varity_R

0.033

gMVP

0.24

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over