Variant 5-38946506-T-C 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.4361A>G(p.Asp1454Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000877 in 1,612,026 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00088 ( 3 hom. )

Consequence

RICTOR
NM_152756.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00

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=0.0112300515).

BS2

High AC in GnomAd4 at 129 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RICTOR	NM_152756.5 linkuse as main transcript	c.4361A>G	p.Asp1454Gly	missense_variant	33/38	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.4361A>G	p.Asp1454Gly	missense_variant	33/38	1	NM_152756.5	ENSP00000349959	P4	Q6R327-1

Frequencies

GnomAD3 genomes

AF:

0.000848

AC:

129

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00126

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000975

AC:

245

AN:

251314

Hom.:

AF XY:

0.000780

AC XY:

106

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00128

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.000880

AC:

1284

AN:

1459718

Hom.:

Cov.:

AF XY:

0.000880

AC XY:

639

AN XY:

726322

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.00119

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000328

Gnomad4 SAS exome

AF:

0.000371

Gnomad4 FIN exome

AF:

0.00159

Gnomad4 NFE exome

AF:

0.000942

Gnomad4 OTH exome

AF:

0.000812

GnomAD4 genome

AF:

0.000847

AC:

129

AN:

152308

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00126

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000940

Hom.:

Bravo

AF:

0.000748

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.000914

AC:

111

EpiCase

AF:

0.00136

EpiControl

AF:

0.000711

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

Aug 17, 2021

The c.4361A>G (p.D1454G) alteration is located in exon 33 (coding exon 33) of the RICTOR gene. This alteration results from a A to G substitution at nucleotide position 4361, causing the aspartic acid (D) at amino acid position 1454 to be replaced by a glycine (G). 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

0.083

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.063

T;.

Eigen

Benign

-0.056

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.11

Sift

Benign

0.55

T;T

Sift4G

Benign

0.29

T;T

Polyphen

0.062

B;B

Vest4

0.56

MVP

0.093

MPC

0.51

ClinPred

0.044

GERP RS

5.2

Varity_R

0.18

gMVP

0.52

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