chr1-38859480-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2PP2BP4_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. 14/21 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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44

Publications

0 publications found

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]

RRAGC Gene-Disease associations (from GenCC):

Long-Olsen-Distelmaier syndrome
Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, G2P

RRAGC links:

ENSG00000273637 (HGNC:):

ENSG00000273637 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 4 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 2.4643 (below the threshold of 3.09). Trascript score misZ: 1.8441 (below the threshold of 3.09). GenCC associations: The gene is linked to Long-Olsen-Distelmaier syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.14676961).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022157.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRAGC	NM_022157.4	MANE Select	c.167G>A	p.Gly56Asp	missense	Exon 1 of 7	NP_071440.1	Q9HB90
	RRAGC	NM_001271851.2		c.167G>A	p.Gly56Asp	missense	Exon 1 of 7	NP_001258780.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RRAGC	ENST00000373001.4	TSL:1 MANE Select	c.167G>A	p.Gly56Asp	missense	Exon 1 of 7	ENSP00000362092.3	Q9HB90
RRAGC	ENST00000865048.1		c.167G>A	p.Gly56Asp	missense	Exon 1 of 7	ENSP00000535107.1
RRAGC	ENST00000865049.1		c.167G>A	p.Gly56Asp	missense	Exon 1 of 7	ENSP00000535108.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1395610

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

688306

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31510

American (AMR)

AF:

0.00

AC:

AN:

35690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25150

East Asian (EAS)

AF:

0.00

AC:

AN:

35722

South Asian (SAS)

AF:

0.00

AC:

AN:

79146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47766

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4218

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1078606

Other (OTH)

AF:

0.00

AC:

AN:

57802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.22

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.55

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

2.4

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

0.80

REVEL

Benign

0.029

Sift

Benign

0.65

Sift4G

Benign

0.65

Polyphen

0.0080

Vest4

0.35

MutPred

0.17

Gain of ubiquitination at K61 (P = 0.0239)

MVP

0.26

MPC

1.0

ClinPred

0.092

GERP RS

1.8

PromoterAI

0.062

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

Varity_R

0.058

gMVP

0.32

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over