Genetic Variant RGPD4:p.Arg229Leu (chr2-107843634-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_182588.3(RGPD4):c.686G>T(p.Arg229Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts 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. R229Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000070 ( 0 hom., cov: 3)

Exomes 𝑓: 0.000041 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

RGPD4
NM_182588.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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: Uncertain_significance. The variant received 0 ACMG points.

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>T	p.Arg229Leu	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>T	p.Arg229Leu	missense	Exon 6 of 23	ENSP00000386810.4	Q7Z3J3-1

Frequencies

GnomAD3 genomes

AF:

0.0000700

AC:

AN:

14286

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:

0.000156

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:

0.0000413

AC:

AN:

241922

Hom.:

Cov.:

AF XY:

0.0000552

AC XY:

AN XY:

126844

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

5586

American (AMR)

AF:

0.00

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:

0.00

AC:

AN:

22754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15270

Middle Eastern (MID)

AF:

0.00

AC:

AN:

746

European-Non Finnish (NFE)

AF:

0.0000645

AC:

AN:

139444

Other (OTH)

AF:

0.0000772

AC:

AN:

12956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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:

0.0000700

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:

0.00

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:

0.000156

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.053

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.49

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0081

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

1.1

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.040

Sift

Benign

0.093

Sift4G

Uncertain

0.0040

Polyphen

0.032

Vest4

0.36

MutPred

0.41

Gain of loop (P = 0.0111)

MVP

0.076

ClinPred

0.11

GERP RS

1.3

Varity_R

0.11

gMVP

0.047

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.31

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.31

Position offset: -49

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over