chr6-89411893-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2

The NM_021244.5(RRAGD):c.101G>T(p.Gly34Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000831 in 1,546,744 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00098 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 2 hom. )

Consequence

RRAGD
NM_021244.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.589

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

hypomagnesemia 7, renal, with or without dilated cardiomyopathy
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
inherited renal tubular disease
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

RRAGD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 6 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 2.1976 (below the threshold of 3.09). Trascript score misZ: 2.3889 (below the threshold of 3.09). GenCC associations: The gene is linked to hypomagnesemia 7, renal, with or without dilated cardiomyopathy.

BP4

Computational evidence support a benign effect (MetaRNN=0.027935386).

BP6

Variant 6-89411893-C-A is Benign according to our data. Variant chr6-89411893-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 2412479.

BS2

High AC in GnomAd4 at 149 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021244.5. 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
	RRAGD	NM_021244.5	MANE Select	c.101G>T	p.Gly34Val	missense	Exon 1 of 7	NP_067067.1	Q9NQL2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RRAGD	ENST00000369415.9	TSL:1 MANE Select	c.101G>T	p.Gly34Val	missense	Exon 1 of 7	ENSP00000358423.4	Q9NQL2-1
RRAGD	ENST00000886444.1		c.101G>T	p.Gly34Val	missense	Exon 2 of 8	ENSP00000556503.1
RRAGD	ENST00000936138.1		c.101G>T	p.Gly34Val	missense	Exon 2 of 8	ENSP00000606197.1

Frequencies

GnomAD3 genomes

AF:

0.000981

AC:

149

AN:

151950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00187

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000604

AC:

AN:

147240

AF XY:

0.000553

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00237

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000815

AC:

1137

AN:

1394678

Hom.:

Cov.:

AF XY:

0.000816

AC XY:

562

AN XY:

688884

show subpopulations

African (AFR)

AF:

0.0000631

AC:

AN:

31706

American (AMR)

AF:

0.000110

AC:

AN:

36434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25154

East Asian (EAS)

AF:

0.0000277

AC:

AN:

36120

South Asian (SAS)

AF:

0.0000376

AC:

AN:

79762

European-Finnish (FIN)

AF:

0.00235

AC:

AN:

41272

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.000918

AC:

992

AN:

1080500

Other (OTH)

AF:

0.000620

AC:

AN:

58026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

129

194

258

323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

<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:

0.000980

AC:

149

AN:

152066

Hom.:

Cov.:

AF XY:

0.000875

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41508

American (AMR)

AF:

0.0000654

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5112

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00189

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00187

AC:

127

AN:

67944

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.00143

Hom.:

Bravo

AF:

0.000502

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000603

AC:

ExAC

AF:

0.000535

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Benign

-0.014

Eigen_PC

Benign

0.088

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.70

M_CAP

Pathogenic

0.68

MetaRNN

Benign

0.028

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.59

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.2

REVEL

Benign

0.077

Sift

Benign

0.10

Sift4G

Uncertain

0.023

Polyphen

0.85

Vest4

0.15

MVP

0.21

MPC

2.0

ClinPred

0.11

GERP RS

3.7

PromoterAI

-0.061

Neutral

(source)

Varity_R

0.23

gMVP

0.25

Mutation Taster

=83/17

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