Variant 2-106413095-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001144013.2(RGPD3):c.5255C>T(p.Ala1752Val) variant causes a missense change. The variant allele was found at a frequency of 0.000132 in 1,610,412 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 1 hom., cov: 28)

Exomes 𝑓: 0.00012 ( 4 hom. )

Consequence

RGPD3
NM_001144013.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.51

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07184246).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD3	NM_001144013.2 link	c.5255C>T	p.Ala1752Val	missense_variant	22/23	ENST00000409886.4	NP_001137485.1	A6NKT7
RGPD3	XM_017004738.2 link	c.5279C>T	p.Ala1760Val	missense_variant	23/24		XP_016860227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD3	ENST00000409886.4 link	c.5255C>T	p.Ala1752Val	missense_variant	22/23	1	NM_001144013.2	ENSP00000386588.4		A6NKT7
RGPD3	ENST00000304514.11 link	c.5237C>T	p.Ala1746Val	missense_variant	22/23	2		ENSP00000303659.8		J3KNE0

Frequencies

GnomAD3 genomes

AF:

0.000212

AC:

AN:

151010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000316

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000196

Gnomad SAS

AF:

0.000651

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000157

AC:

AN:

249164

Hom.:

AF XY:

0.000170

AC XY:

AN XY:

135208

show subpopulations

Gnomad AFR exome

AF:

0.000517

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000296

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000169

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000124

AC:

181

AN:

1459292

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

108

AN XY:

725936

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000430

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000105

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000212

AC:

AN:

151120

Hom.:

Cov.:

AF XY:

0.000244

AC XY:

AN XY:

73696

show subpopulations

Gnomad4 AFR

AF:

0.000315

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000197

Gnomad4 SAS

AF:

0.000652

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000347

Hom.:

Bravo

AF:

0.000268

ExAC

AF:

0.000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.5255C>T (p.A1752V) alteration is located in exon 22 (coding exon 22) of the RGPD3 gene. This alteration results from a C to T substitution at nucleotide position 5255, causing the alanine (A) at amino acid position 1752 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0029

.;T

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.0024

MetaRNN

Benign

0.072

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.3

.;L

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.17

.;N

REVEL

Benign

0.099

Sift

Pathogenic

0.0

.;D

Sift4G

Benign

0.13

T;D

Polyphen

0.0030

.;B

Vest4

0.30

MVP

0.030

ClinPred

0.11

GERP RS

0.17

Varity_R

0.12

gMVP

0.094

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over