Genetic Variant RGPD3:p.Gln1703Pro (chr2-106413242-T-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001144013.2(RGPD3):c.5108A>C(p.Gln1703Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000454 in 1,611,996 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. Q1703R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00032 ( 1 hom., cov: 29)

Exomes 𝑓: 0.00047 ( 4 hom. )

Consequence

RGPD3
NM_001144013.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.27

Publications

2 publications found

Variant links:

Genes affected

RGPD3 (HGNC:32416): (RANBP2 like and GRIP domain containing 3) This gene is located in a cluster of Ran-binding protein related genes on chromosome 2 which arose through duplication in primates. The encoded protein contains an N-terminal TPR (tetratricopeptide repeat) domain, two Ran-binding domains, and a C-terminal GRIP domain (golgin-97, RanBP2alpha, Imh1p and p230/golgin-245) domain. [provided by RefSeq, Sep 2011]

RGPD3 links:

ENSG00000291125 (HGNC:):

ENSG00000291125 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.005361259).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGPD3	NM_001144013.2 link	c.5108A>C	p.Gln1703Pro	missense_variant	Exon 22 of 23	ENST00000409886.4	NP_001137485.1	A6NKT7
RGPD3	XM_017004738.2 link	c.5132A>C	p.Gln1711Pro	missense_variant	Exon 23 of 24		XP_016860227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGPD3	ENST00000409886.4 link	c.5108A>C	p.Gln1703Pro	missense_variant	Exon 22 of 23	1	NM_001144013.2	ENSP00000386588.4		A6NKT7

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152184

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:

0.00955

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000988

AC:

248

AN:

251086

AF XY:

0.00132

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000469

AC:

684

AN:

1459696

Hom.:

Cov.:

AF XY:

0.000662

AC XY:

481

AN XY:

726156

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33406

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00713

AC:

614

AN:

86160

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.0000279

AC:

AN:

1111824

Other (OTH)

AF:

0.000598

AC:

AN:

60206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

Heterozygous variant carriers

148

198

247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000315

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41578

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00956

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.407

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000171

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.00119

AC:

144

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.0026

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.88

D;D

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N

PhyloP100

4.3

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.31

.;N

REVEL

Benign

0.15

Sift

Benign

0.053

.;T

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.0010

.;B

Vest4

0.45

MutPred

0.14

.;Loss of helix (P = 0.0104);

MVP

0.030

ClinPred

0.028

GERP RS

-0.035

Varity_R

0.12

gMVP

0.21

Mutation Taster

=100/0

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

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2-106413242-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over