1-38859483-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_022157.4(RRAGC):c.164G>A(p.Gly55Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000349 in 1,547,972 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. 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. G55R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

RRAGC
NM_022157.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.06

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

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=0.11449966).

BS2

High AC in GnomAd4 at 15 AD gene.

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.164G>A	p.Gly55Glu	missense	Exon 1 of 7	NP_071440.1	Q9HB90
	RRAGC	NM_001271851.2		c.164G>A	p.Gly55Glu	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.164G>A	p.Gly55Glu	missense	Exon 1 of 7	ENSP00000362092.3	Q9HB90
RRAGC	ENST00000865048.1		c.164G>A	p.Gly55Glu	missense	Exon 1 of 7	ENSP00000535107.1
RRAGC	ENST00000865049.1		c.164G>A	p.Gly55Glu	missense	Exon 1 of 7	ENSP00000535108.1

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000137

AC:

AN:

146470

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000407

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000935

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000279

AC:

AN:

1395740

Hom.:

Cov.:

AF XY:

0.0000334

AC XY:

AN XY:

688372

show subpopulations

African (AFR)

AF:

0.000127

AC:

AN:

31526

American (AMR)

AF:

0.0000560

AC:

AN:

35692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25156

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35728

South Asian (SAS)

AF:

0.00

AC:

AN:

79148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47774

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4228

European-Non Finnish (NFE)

AF:

0.0000297

AC:

AN:

1078686

Other (OTH)

AF:

0.00

AC:

AN:

57802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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

AF:

0.0000985

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41564

American (AMR)

AF:

0.000261

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67980

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000718

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.22

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.56

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

2.1

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.50

REVEL

Benign

0.040

Sift

Benign

0.16

Sift4G

Benign

0.097

Polyphen

0.0

Vest4

0.20

MutPred

0.18

Gain of solvent accessibility (P = 0.024)

MVP

0.14

MPC

1.0

ClinPred

0.021

GERP RS

1.7

PromoterAI

0.049

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

Varity_R

0.064

gMVP

0.34

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over