Variant 5-38955694-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152756.5(RICTOR):c.2510C>T(p.Ser837Phe) variant causes a missense change. The variant allele was found at a frequency of 0.394 in 1,561,666 control chromosomes in the GnomAD database, including 123,135 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.38 ( 11091 hom., cov: 32)

Exomes 𝑓: 0.40 ( 112044 hom. )

Consequence

RICTOR
NM_152756.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.21

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.254349E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RICTOR	NM_152756.5 linkuse as main transcript	c.2510C>T	p.Ser837Phe	missense_variant	26/38	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.2510C>T	p.Ser837Phe	missense_variant	26/38	1	NM_152756.5	ENSP00000349959	P4	Q6R327-1

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57278

AN:

151686

Hom.:

11095

Cov.:

show subpopulations

Gnomad AFR

AF:

0.290

Gnomad AMI

AF:

0.346

Gnomad AMR

AF:

0.388

Gnomad ASJ

AF:

0.424

Gnomad EAS

AF:

0.473

Gnomad SAS

AF:

0.344

Gnomad FIN

AF:

0.468

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.409

Gnomad OTH

AF:

0.363

GnomAD3 exomes

AF:

0.394

AC:

98534

AN:

250376

Hom.:

19893

AF XY:

0.391

AC XY:

52952

AN XY:

135304

show subpopulations

Gnomad AFR exome

AF:

0.283

Gnomad AMR exome

AF:

0.379

Gnomad ASJ exome

AF:

0.426

Gnomad EAS exome

AF:

0.468

Gnomad SAS exome

AF:

0.314

Gnomad FIN exome

AF:

0.468

Gnomad NFE exome

AF:

0.407

Gnomad OTH exome

AF:

0.381

GnomAD4 exome

AF:

0.395

AC:

557358

AN:

1409860

Hom.:

112044

Cov.:

AF XY:

0.394

AC XY:

277218

AN XY:

704152

show subpopulations

Gnomad4 AFR exome

AF:

0.281

Gnomad4 AMR exome

AF:

0.378

Gnomad4 ASJ exome

AF:

0.427

Gnomad4 EAS exome

AF:

0.493

Gnomad4 SAS exome

AF:

0.314

Gnomad4 FIN exome

AF:

0.466

Gnomad4 NFE exome

AF:

0.399

Gnomad4 OTH exome

AF:

0.383

GnomAD4 genome

AF:

0.377

AC:

57283

AN:

151806

Hom.:

11091

Cov.:

AF XY:

0.383

AC XY:

28417

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.290

Gnomad4 AMR

AF:

0.388

Gnomad4 ASJ

AF:

0.424

Gnomad4 EAS

AF:

0.473

Gnomad4 SAS

AF:

0.342

Gnomad4 FIN

AF:

0.468

Gnomad4 NFE

AF:

0.409

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.400

Hom.:

32255

Bravo

AF:

0.367

TwinsUK

AF:

0.418

AC:

1550

ALSPAC

AF:

0.411

AC:

1584

ESP6500AA

AF:

0.285

AC:

1257

ESP6500EA

AF:

0.401

AC:

3449

ExAC

AF:

0.393

AC:

47694

Asia WGS

AF:

0.352

AC:

1224

AN:

3478

EpiCase

AF:

0.397

EpiControl

AF:

0.397

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.040

T;.

Eigen

Benign

-0.17

Eigen_PC

Benign

0.022

FATHMM_MKL

Benign

0.67

LIST_S2

Pathogenic

0.98

D;D

MetaRNN

Benign

0.00083

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.49

N;N

MutationTaster

Benign

0.43

P;P

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.33

N;N

REVEL

Benign

0.049

Sift

Benign

0.70

T;T

Sift4G

Uncertain

0.041

D;D

Polyphen

0.0020

B;B

Vest4

0.41

MPC

0.46

ClinPred

0.014

GERP RS

4.8

Varity_R

0.19

gMVP

0.21

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over