Variant 6-89387383-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PS1_ModeratePM2PM5PP3_StrongPP5_Moderate

The NM_021244.5(RRAGD):c.356C>G(p.Pro119Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P119L) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)

Consequence

RRAGD
NM_021244.5 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 9.60

Variant links:

Genes affected

RRAGD (HGNC:19903): (Ras related GTP binding D) RRAGD is a monomeric guanine nucleotide-binding protein, or G protein. By binding GTP or GDP, small G proteins act as molecular switches in numerous cell processes and signaling pathways.[supplied by OMIM, Apr 2004]

RRAGD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PS1

Transcript NM_021244.5 (RRAGD) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chrnull-null-null-null is described in UniProt as null.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.976

PP5

Variant 6-89387383-G-C is Pathogenic according to our data. Variant chr6-89387383-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 1335637.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRAGD	NM_021244.5 link	c.356C>G	p.Pro119Arg	missense_variant	2/7	ENST00000369415.9	NP_067067.1	Q9NQL2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RRAGD	ENST00000369415.9 link	c.356C>G	p.Pro119Arg	missense_variant	2/7	1	NM_021244.5	ENSP00000358423.4	Q9NQL2-1
RRAGD	ENST00000359203.3 link	c.-9-7016C>G		intron_variant		2		ENSP00000352131.2	Q9NQL2-2
RRAGD	ENST00000492783.1 link	n.380C>G		non_coding_transcript_exon_variant	2/5	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HYPOMAGNESEMIA 7, RENAL, WITH DILATED CARDIOMYOPATHY

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 08, 2022

- -

not provided

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.47

BayesDel_noAF

Pathogenic

0.43

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.70

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.98

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.29

MetaRNN

Pathogenic

0.98

MetaSVM

Pathogenic

0.85

MutationAssessor

Pathogenic

3.4

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-8.5

REVEL

Pathogenic

0.92

Sift

Pathogenic

0.0

Sift4G

Benign

0.082

Polyphen

1.0

Vest4

0.94

MutPred

0.90

Gain of helix (P = 0.062);

MVP

0.94

MPC

1.9

ClinPred

1.0

GERP RS

5.5

Varity_R

0.95

gMVP

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over