2-106415911-T-C

Variant summary

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

The NM_001144013.2(RGPD3):​c.5003A>G​(p.His1668Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 27)

Consequence

RGPD3
NM_001144013.2 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.15

Publications

0 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]

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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=0.19564545).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RGPD3NM_001144013.2 linkc.5003A>G p.His1668Arg missense_variant Exon 21 of 23 ENST00000409886.4 NP_001137485.1 A6NKT7
RGPD3XM_017004738.2 linkc.5027A>G p.His1676Arg missense_variant Exon 22 of 24 XP_016860227.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RGPD3ENST00000409886.4 linkc.5003A>G p.His1668Arg missense_variant Exon 21 of 23 1 NM_001144013.2 ENSP00000386588.4 A6NKT7

Frequencies

GnomAD3 genomes
Cov.:
27
GnomAD4 exome
Cov.:
40
GnomAD4 genome
Cov.:
27

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 05, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.5003A>G (p.H1668R) alteration is located in exon 21 (coding exon 21) of the RGPD3 gene. This alteration results from a A to G substitution at nucleotide position 5003, causing the histidine (H) at amino acid position 1668 to be replaced by an arginine (R). 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
0.079
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
19
DANN
Benign
0.59
DEOGEN2
Benign
0.0020
.;T
Eigen
Benign
-0.13
Eigen_PC
Benign
-0.27
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.69
T;T
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.20
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Uncertain
2.2
.;M
PhyloP100
5.1
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
0.30
.;N
REVEL
Benign
0.16
Sift
Benign
0.40
.;T
Sift4G
Benign
0.067
T;D
Polyphen
0.95
.;P
Vest4
0.65
MutPred
0.35
.;Gain of MoRF binding (P = 0.0132);
MVP
0.11
ClinPred
0.41
T
GERP RS
0.70
Varity_R
0.035
gMVP
0.050
Mutation Taster
=98/2
polymorphism

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

Other links and lift over

hg19: chr2-107032367; API