1-38859480-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022157.4(RRAGC):​c.167G>A​(p.Gly56Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,395,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RRAGC
NM_022157.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44
Variant links:
Genes affected
RRAGC (HGNC:19902): (Ras related GTP binding C) This gene encodes a member of the GTR/RAG GTP-binding protein family. The encoded protein is a monomeric guanine nucleotide-binding protein which forms a heterodimer with RRAGA and RRAGB and is primarily localized to the cytoplasm. The encoded protein promotes intracellular localization of the mTOR complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14676961).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RRAGCNM_022157.4 linkc.167G>A p.Gly56Asp missense_variant Exon 1 of 7 ENST00000373001.4 NP_071440.1 Q9HB90
RRAGCNM_001271851.2 linkc.167G>A p.Gly56Asp missense_variant Exon 1 of 7 NP_001258780.1 Q9HB90B4DQ03B4DQG4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RRAGCENST00000373001.4 linkc.167G>A p.Gly56Asp missense_variant Exon 1 of 7 1 NM_022157.4 ENSP00000362092.3 Q9HB90
ENSG00000273637ENST00000622355.1 linkn.989-2398G>A intron_variant Intron 6 of 11 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000215
AC:
3
AN:
1395610
Hom.:
0
Cov.:
37
AF XY:
0.00000145
AC XY:
1
AN XY:
688306
show subpopulations
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:
0.00000278
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000113

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Sep 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.167G>A (p.G56D) alteration is located in exon 1 (coding exon 1) of the RRAGC gene. This alteration results from a G to A substitution at nucleotide position 167, causing the glycine (G) at amino acid position 56 to be replaced by an aspartic acid (D). 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
0.18
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
22
DANN
Benign
0.85
DEOGEN2
Benign
0.22
T
Eigen
Benign
-0.99
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.63
D
LIST_S2
Benign
0.55
T
M_CAP
Pathogenic
0.46
D
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.0
N
PrimateAI
Pathogenic
0.94
D
PROVEAN
Benign
0.80
N
REVEL
Benign
0.029
Sift
Benign
0.65
T
Sift4G
Benign
0.65
T
Polyphen
0.0080
B
Vest4
0.35
MutPred
0.17
Gain of ubiquitination at K61 (P = 0.0239);
MVP
0.26
MPC
1.0
ClinPred
0.092
T
GERP RS
1.8
RBP_binding_hub_radar
1.0
RBP_regulation_power_radar
2.7
Varity_R
0.058
gMVP
0.32

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.

Other links and lift over

dbSNP: rs926352152; hg19: chr1-39325152; API