Variant 2-106413137-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 ENST00000409886.4(RGPD3):c.5213C>T(p.Thr1738Met) variant causes a missense change. The variant allele was found at a frequency of 0.000274 in 1,611,370 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00027 ( 4 hom. )

Consequence

RGPD3
ENST00000409886.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.65

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=0.13255796).

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 linkuse as main transcript	c.5213C>T	p.Thr1738Met	missense_variant	22/23	ENST00000409886.4	NP_001137485.1	A6NKT7
RGPD3	XM_017004738.2 linkuse as main transcript	c.5237C>T	p.Thr1746Met	missense_variant	23/24		XP_016860227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD3	ENST00000409886.4 linkuse as main transcript	c.5213C>T	p.Thr1738Met	missense_variant	22/23	1	NM_001144013.2	ENSP00000386588.4		A6NKT7
RGPD3	ENST00000304514.11 linkuse as main transcript	c.5195C>T	p.Thr1732Met	missense_variant	22/23	2		ENSP00000303659.8		J3KNE0

Frequencies

GnomAD3 genomes

AF:

0.000264

AC:

AN:

151792

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

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:

0.000265

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000216

AC:

AN:

249810

Hom.:

AF XY:

0.000222

AC XY:

AN XY:

135370

show subpopulations

Gnomad AFR exome

AF:

0.0000639

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000248

Gnomad OTH exome

AF:

0.000659

GnomAD4 exome

AF:

0.000275

AC:

401

AN:

1459464

Hom.:

Cov.:

AF XY:

0.000236

AC XY:

171

AN XY:

726022

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000312

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

AF:

0.000263

AC:

AN:

151906

Hom.:

Cov.:

AF XY:

0.000310

AC XY:

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.000391

Hom.:

Bravo

AF:

0.000317

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000634

AC:

ExAC

AF:

0.000124

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

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

Feb 22, 2023

The c.5213C>T (p.T1738M) 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 5213, causing the threonine (T) at amino acid position 1738 to be replaced by a methionine (M). 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

0.14

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0042

.;T

Eigen

Benign

-0.039

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.4

.;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.53

.;N

REVEL

Benign

0.19

Sift

Pathogenic

0.0

.;D

Sift4G

Uncertain

0.015

D;D

Polyphen

0.99

.;D

Vest4

0.52

MVP

0.11

ClinPred

0.13

GERP RS

0.13

Varity_R

0.13

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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