Variant 2-106413143-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000409886.4(RGPD3):c.5207T>C(p.Ile1736Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,611,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

RGPD3
ENST00000409886.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.89

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.829

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD3	NM_001144013.2 linkuse as main transcript	c.5207T>C	p.Ile1736Thr	missense_variant	22/23	ENST00000409886.4	NP_001137485.1	A6NKT7
RGPD3	XM_017004738.2 linkuse as main transcript	c.5231T>C	p.Ile1744Thr	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.5207T>C	p.Ile1736Thr	missense_variant	22/23	1	NM_001144013.2	ENSP00000386588.4		A6NKT7
RGPD3	ENST00000304514.11 linkuse as main transcript	c.5189T>C	p.Ile1730Thr	missense_variant	22/23	2		ENSP00000303659.8		J3KNE0

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000525

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

249834

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135374

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1459524

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726056

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000855

AC:

AN:

151996

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74210

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000525

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.0000165

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

Nov 18, 2023

The c.5207T>C (p.I1736T) alteration is located in exon 22 (coding exon 22) of the RGPD3 gene. This alteration results from a T to C substitution at nucleotide position 5207, causing the isoleucine (I) at amino acid position 1736 to be replaced by a threonine (T). 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

Pathogenic

0.61

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0034

.;T

Eigen

Benign

0.14

Eigen_PC

Benign

-0.033

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.0053

MetaRNN

Pathogenic

0.83

D;D

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.2

.;M

MutationTaster

Benign

0.96

N;N

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

0.090

.;N

REVEL

Benign

0.22

Sift

Pathogenic

0.0

.;D

Sift4G

Uncertain

0.049

D;D

Polyphen

0.98

.;D

Vest4

0.83

MutPred

0.80

.;Gain of disorder (P = 0.0341);

MVP

0.20

ClinPred

0.55

GERP RS

1.1

Varity_R

0.18

gMVP

0.26

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