5-38955694-G-C

Position:

• chr5-38955694-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000357387.8(RICTOR):​c.2510C>G​(p.Ser837Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,418,158 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S837F) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RICTOR ENST00000357387.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.21

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2850923).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RICTOR	NM_152756.5	c.2510C>G	p.Ser837Cys	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	c.2510C>G	p.Ser837Cys	missense_variant	26/38	1	NM_152756.5	ENSP00000349959	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1418158 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 708088

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000187

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	0.092
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.55	N;N
MutationTaster	Benign	0.83	P;P
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.17
Sift	Benign	0.18	T;T
Sift4G	Uncertain	0.020	D;D
Polyphen		0.69	P;P
Vest4		0.37
MutPred		0.58		Gain of methylation at K838 (P = 0.0137);Gain of methylation at K838 (P = 0.0137);
MVP		0.13
MPC		0.74
ClinPred		0.66	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.17

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

Other links and lift over

dbSNP: rs2043112; hg19: chr5-38955796;