dbSNP rs767496590: RGPD4:p.Ser18Phe (chr2-107827066-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182588.3(RGPD4):c.53C>T(p.Ser18Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000032 in 1,592,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 35)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

RGPD4
NM_182588.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20

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:

RGPD4-AS1 (HGNC:49273): (RGPD4 antisense RNA 1 (head to head))

RGPD4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1807608).

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.53C>T	p.Ser18Phe	missense	Exon 1 of 23	NP_872394.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RGPD4	ENST00000408999.4	TSL:1 MANE Select	c.53C>T	p.Ser18Phe	missense	Exon 1 of 23	ENSP00000386810.4	Q7Z3J3-1
RGPD4-AS1	ENST00000457647.2	TSL:1	n.-175G>A		upstream_gene	N/A
RGPD4-AS1	ENST00000417284.3	TSL:2	n.-237G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000331

AC:

AN:

211478

AF XY:

0.0000526

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000643

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000539

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000305

AC:

AN:

1440716

Hom.:

Cov.:

AF XY:

0.0000350

AC XY:

AN XY:

714614

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32990

American (AMR)

AF:

0.0000474

AC:

AN:

42220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25612

East Asian (EAS)

AF:

0.00

AC:

AN:

38936

South Asian (SAS)

AF:

0.00

AC:

AN:

82738

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51486

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4124

European-Non Finnish (NFE)

AF:

0.0000381

AC:

AN:

1103026

Other (OTH)

AF:

0.00

AC:

AN:

59584

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

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

AF:

0.0000460

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41432

American (AMR)

AF:

0.000131

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000565

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000167

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

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.013

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.77

M_CAP

Benign

0.0095

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

2.2

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.085

Sift

Uncertain

0.021

Sift4G

Uncertain

0.0070

Polyphen

0.84

Vest4

0.26

MutPred

0.28

Loss of disorder (P = 0.0039)

MVP

0.055

ClinPred

0.16

GERP RS

1.4

PromoterAI

-0.078

Neutral

(source)

Varity_R

0.084

gMVP

0.012

Mutation Taster

=98/2

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