Genetic Variant RGPD4:p.Arg229Gln (chr2-107843634-G-A) – 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.686G>A(p.Arg229Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 3)

Exomes 𝑓: 0.000099 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

RGPD4
NM_182588.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

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=0.06301698).

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.686G>A	p.Arg229Gln	missense	Exon 6 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.686G>A	p.Arg229Gln	missense	Exon 6 of 23	ENSP00000386810.4	Q7Z3J3-1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

14286

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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:

0.000312

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

3278

AF XY:

0.00

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000992

AC:

AN:

241922

Hom.:

Cov.:

AF XY:

0.0000867

AC XY:

AN XY:

126844

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

5586

American (AMR)

AF:

0.000574

AC:

AN:

13948

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4918

East Asian (EAS)

AF:

0.00

AC:

AN:

26300

South Asian (SAS)

AF:

0.0000439

AC:

AN:

22754

European-Finnish (FIN)

AF:

0.000131

AC:

AN:

15270

Middle Eastern (MID)

AF:

0.00

AC:

AN:

746

European-Non Finnish (NFE)

AF:

0.0000574

AC:

AN:

139444

Other (OTH)

AF:

0.000386

AC:

AN:

12956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.610

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000210

AC:

AN:

14286

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

6566

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

2898

American (AMR)

AF:

0.000524

AC:

AN:

1908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

278

East Asian (EAS)

AF:

0.00

AC:

AN:

1544

South Asian (SAS)

AF:

0.00

AC:

AN:

316

European-Finnish (FIN)

AF:

0.00

AC:

AN:

598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000312

AC:

AN:

6420

Other (OTH)

AF:

0.00

AC:

AN:

176

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

Alfa

AF:

0.00

Hom.:

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

0.083

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0077

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.76

M_CAP

Benign

0.0046

MetaRNN

Benign

0.063

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

1.1

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.7

REVEL

Benign

0.042

Sift

Benign

0.13

Sift4G

Benign

0.068

Polyphen

0.0

Vest4

0.10

MVP

0.040

ClinPred

0.083

GERP RS

1.3

Varity_R

0.066

gMVP

0.019

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over