1-38859487-G-C

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.160C>G(p.Pro54Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000271 in 1,547,796 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. P54S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

RRAGC
NM_022157.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.24

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=0.14398664).

BS2

High AC in GnomAdExome4 at 41 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.160C>G	p.Pro54Ala	missense	Exon 1 of 7	NP_071440.1	Q9HB90
	RRAGC	NM_001271851.2		c.160C>G	p.Pro54Ala	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.160C>G	p.Pro54Ala	missense	Exon 1 of 7	ENSP00000362092.3	Q9HB90
RRAGC	ENST00000865048.1		c.160C>G	p.Pro54Ala	missense	Exon 1 of 7	ENSP00000535107.1
RRAGC	ENST00000865049.1		c.160C>G	p.Pro54Ala	missense	Exon 1 of 7	ENSP00000535108.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

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

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1395686

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

688344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31524

American (AMR)

AF:

0.00

AC:

AN:

35692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25156

East Asian (EAS)

AF:

0.0000560

AC:

AN:

35726

South Asian (SAS)

AF:

0.00

AC:

AN:

79146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47752

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4206

European-Non Finnish (NFE)

AF:

0.0000352

AC:

AN:

1078684

Other (OTH)

AF:

0.0000173

AC:

AN:

57800

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

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:

0.00000657

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67980

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.24

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.55

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

1.2

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.51

REVEL

Benign

0.034

Sift

Benign

0.24

Sift4G

Benign

0.54

Polyphen

0.0

Vest4

0.15

MutPred

0.21

Gain of catalytic residue at P54 (P = 0.0161)

MVP

0.29

MPC

0.74

ClinPred

0.061

GERP RS

1.8

PromoterAI

0.0088

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Varity_R

0.023

gMVP

0.21

Mutation Taster

=88/12

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

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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