Genetic Variant RGPD4:p.Arg198Cys (chr2-107843195-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_182588.3(RGPD4):c.592C>T(p.Arg198Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0024 ( 19 hom. )

Failed GnomAD Quality Control

Consequence

RGPD4
NM_182588.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.842

Publications

0 publications found

Variant links:

Genes affected

RGPD4 (HGNC:32417): (RANBP2 like and GRIP domain containing 4) Predicted to contribute to GTPase activator activity. Predicted to be involved in NLS-bearing protein import into nucleus. Predicted to be part of nuclear pore. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RGPD4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009821892).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182588.3. 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
	RGPD4	NM_182588.3	MANE Select	c.592C>T	p.Arg198Cys	missense	Exon 5 of 23	NP_872394.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGPD4	ENST00000408999.4	TSL:1 MANE Select	c.592C>T	p.Arg198Cys	missense	Exon 5 of 23	ENSP00000386810.4	Q7Z3J3-1

Frequencies

GnomAD3 genomes

AF:

0.000390

AC:

AN:

5128

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:

0.00339

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00284

AC:

AN:

1762

AF XY:

0.00111

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00801

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00240

AC:

161

AN:

67008

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

AN XY:

34928

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

1474

American (AMR)

AF:

0.00

AC:

AN:

5138

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1230

East Asian (EAS)

AF:

0.0112

AC:

146

AN:

13018

South Asian (SAS)

AF:

0.00141

AC:

AN:

5688

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

140

European-Non Finnish (NFE)

AF:

0.0000918

AC:

AN:

32690

Other (OTH)

AF:

0.00114

AC:

AN:

3520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000388

AC:

AN:

5156

Hom.:

Cov.:

AF XY:

0.000820

AC XY:

AN XY:

2440

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

868

American (AMR)

AF:

0.00

AC:

AN:

880

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00340

AC:

AN:

588

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

2154

Other (OTH)

AF:

0.00

AC:

AN:

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:

0.000169

Hom.:

ExAC

AF:

0.000197

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.087

Eigen

Benign

0.044

Eigen_PC

Benign

-0.073

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.019

MetaRNN

Benign

0.0098

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

0.84

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.16

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.18

MutPred

0.39

Loss of solvent accessibility (P = 0.0146)

MVP

0.37

ClinPred

0.26

GERP RS

1.6

Varity_R

0.26

gMVP

0.053

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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