7-151519465-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005614.4(RHEB):​c.47C>T​(p.Ser16Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RHEB
NM_005614.4 missense

Scores

5
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.97
Variant links:
Genes affected
RHEB (HGNC:10011): (Ras homolog, mTORC1 binding) This gene is a member of the small GTPase superfamily and encodes a lipid-anchored, cell membrane protein with five repeats of the RAS-related GTP-binding region. This protein is vital in regulation of growth and cell cycle progression due to its role in the insulin/TOR/S6K signaling pathway. The protein has GTPase activity and shuttles between a GDP-bound form and a GTP-bound form, and farnesylation of the protein is required for this activity. Three pseudogenes have been mapped, two on chromosome 10 and one on chromosome 22. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RHEBNM_005614.4 linkuse as main transcriptc.47C>T p.Ser16Phe missense_variant 1/8 ENST00000262187.10 NP_005605.1 Q15382A0A090N900
RHEBXM_011516457.3 linkuse as main transcriptc.-79C>T 5_prime_UTR_premature_start_codon_gain_variant 1/9 XP_011514759.1
RHEBXM_011516457.3 linkuse as main transcriptc.-79C>T 5_prime_UTR_variant 1/9 XP_011514759.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RHEBENST00000262187.10 linkuse as main transcriptc.47C>T p.Ser16Phe missense_variant 1/81 NM_005614.4 ENSP00000262187.5 Q15382
RHEBENST00000496004.5 linkuse as main transcriptc.-264+433C>T intron_variant 2 ENSP00000418161.1 C9J931
RHEBENST00000478470.5 linkuse as main transcriptn.47C>T non_coding_transcript_exon_variant 1/95 ENSP00000417802.1 F8WBL3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1380312
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
685772
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Seizure;C4022738:Neurodevelopmental delay Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInstitute of Human Genetics, University of Leipzig Medical CenterSep 30, 2021This variant was identified as de novo (maternity and paternity confirmed). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.94
BayesDel_addAF
Uncertain
0.096
D
BayesDel_noAF
Benign
-0.10
CADD
Pathogenic
27
DANN
Uncertain
0.98
DEOGEN2
Pathogenic
0.84
D
Eigen
Benign
-0.075
Eigen_PC
Benign
-0.039
FATHMM_MKL
Benign
0.63
D
LIST_S2
Uncertain
0.96
D
M_CAP
Pathogenic
0.97
D
MetaRNN
Uncertain
0.62
D
MetaSVM
Uncertain
-0.22
T
MutationAssessor
Benign
1.7
L
PrimateAI
Pathogenic
0.85
D
PROVEAN
Pathogenic
-4.6
D
REVEL
Uncertain
0.62
Sift
Uncertain
0.029
D
Sift4G
Uncertain
0.023
D
Polyphen
0.16
B
Vest4
0.37
MutPred
0.71
Loss of phosphorylation at S16 (P = 0.0431);
MVP
0.90
MPC
1.4
ClinPred
0.77
D
GERP RS
2.9
Varity_R
0.68
gMVP
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs1803142082; hg19: chr7-151216551; COSMIC: COSV51262962; COSMIC: COSV51262962; API