rs2043112

Variant names:

• chr5-38955694-G-A
• rs2043112
• NM_152756.5:c.2510C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-38955694-G-A
• chr5-38955694-G-C
• chr5-38955694-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PP2 BP4_Strong BA1

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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.38 (11091 hom., cov: 32)
  • Exomes 𝑓: 0.40 (112044 hom.)
• Consequence: RICTOR NM_152756.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.21
• Publications: 59 publications found

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 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 3.0542 (below the threshold of 3.09). Trascript score misZ: 2.7182 (below the threshold of 3.09). GenCC associations: The gene is linked to Tourette syndrome.
• 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 rank	MANE	Protein	UniProt
RICTOR	NM_152756.5	c.2510C>T	p.Ser837Phe	missense_variant	Exon 26 of 38	ENST00000357387.8	NP_689969.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RICTOR	ENST00000357387.8	c.2510C>T	p.Ser837Phe	missense_variant	Exon 26 of 38	1	NM_152756.5	ENSP00000349959.3

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57278 AN: 151686 Hom.: 11095 Cov.: 32

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

GnomAD2 exomes AF: 0.394 AC: 98534 AN: 250376 AF XY: 0.391

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 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.: 25 AF XY: 0.394 AC XY: 277218 AN XY: 704152

African (AFR) AF: 0.281 AC: 9147 AN: 32532

American (AMR) AF: 0.378 AC: 16858 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 11005 AN: 25750

East Asian (EAS) AF: 0.493 AC: 19427 AN: 39390

South Asian (SAS) AF: 0.314 AC: 26745 AN: 85228

European-Finnish (FIN) AF: 0.466 AC: 24859 AN: 53320

Middle Eastern (MID) AF: 0.323 AC: 1832 AN: 5680

European-Non Finnish (NFE) AF: 0.399 AC: 425042 AN: 1064804

Other (OTH) AF: 0.383 AC: 22443 AN: 58580

GnomAD4 genome AF: 0.377 AC: 57283 AN: 151806 Hom.: 11091 Cov.: 32 AF XY: 0.383 AC XY: 28417 AN XY: 74198

African (AFR) AF: 0.290 AC: 12003 AN: 41438

American (AMR) AF: 0.388 AC: 5907 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1471 AN: 3468

East Asian (EAS) AF: 0.473 AC: 2440 AN: 5154

South Asian (SAS) AF: 0.342 AC: 1647 AN: 4816

European-Finnish (FIN) AF: 0.468 AC: 4931 AN: 10544

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27712 AN: 67826

Other (OTH) AF: 0.361 AC: 764 AN: 2114

Alfa AF: 0.394 Hom.: 47422

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	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Benign	0.64
DEOGEN2	Benign	0.040	T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	0.022
FATHMM_MKL	Benign	0.67	D
LIST_S2	Pathogenic	0.98	D;D
MetaRNN	Benign	0.00083	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.49	N;N
PhyloP100		4.2
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.33	N;N
REVEL	Benign	0.049
Sift	Benign	0.70	T;T
Sift4G	Uncertain	0.041	D;D
Vest4		0.41
ClinPred		0.014	T
GERP RS		4.8
Varity_R		0.19
gMVP		0.21
Mutation Taster		=98/2	polymorphism (auto)

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: rs2043112; hg19: chr5-38955796; COSMIC: COSV57117211;