2-86974160-G-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001382344.1(RGPD1):​c.1361G>A​(p.Arg454Gln) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000030 ( 0 hom., cov: 18)
Exomes 𝑓: 0.000038 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RGPD1
NM_001382344.1 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.96
Variant links:
Genes affected
RGPD1 (HGNC:32414): (RANBP2 like and GRIP domain containing 1) Predicted to contribute to GTPase activator activity. Predicted to be involved in NLS-bearing protein import into nucleus. Predicted to be part of nuclear pore. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.31476337).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RGPD1NM_001382344.1 linkuse as main transcriptc.1361G>A p.Arg454Gln missense_variant 10/23 ENST00000641458.2 NP_001369273.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RGPD1ENST00000641458.2 linkuse as main transcriptc.1361G>A p.Arg454Gln missense_variant 10/23 NM_001382344.1 ENSP00000492954 A2
RGPD1ENST00000398193.8 linkuse as main transcriptc.1361G>A p.Arg454Gln missense_variant 10/231 ENSP00000381253 P4

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
4
AN:
135118
Hom.:
0
Cov.:
18
FAILED QC
Gnomad AFR
AF:
0.0000845
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000160
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000379
AC:
55
AN:
1452090
Hom.:
0
Cov.:
30
AF XY:
0.0000374
AC XY:
27
AN XY:
721988
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000466
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000407
Gnomad4 OTH exome
AF:
0.0000501
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000296
AC:
4
AN:
135118
Hom.:
0
Cov.:
18
AF XY:
0.0000613
AC XY:
4
AN XY:
65240
show subpopulations
Gnomad4 AFR
AF:
0.0000845
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000160
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000122
Hom.:
0

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 submitterclinical testingAmbry GeneticsDec 07, 2021The c.1337G>A (p.R446Q) alteration is located in exon 10 (coding exon 10) of the RGPD1 gene. This alteration results from a G to A substitution at nucleotide position 1337, causing the arginine (R) at amino acid position 446 to be replaced by a glutamine (Q). 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
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.057
T;.;T;.
Eigen
Uncertain
0.22
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.86
D;D;.;D
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.31
T;T;T;T
MetaSVM
Benign
-0.84
T
MutationAssessor
Uncertain
2.7
M;.;M;.
MutationTaster
Benign
0.79
N;N;N
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-2.2
N;N;N;.
REVEL
Benign
0.14
Sift
Benign
0.13
T;T;T;.
Sift4G
Uncertain
0.0040
D;D;D;.
Polyphen
1.0
.;D;.;.
Vest4
0.34
MutPred
0.41
.;Loss of loop (P = 0.0022);.;Loss of loop (P = 0.0022);
MVP
0.15
ClinPred
0.89
D
GERP RS
2.3
Varity_R
0.17
gMVP
0.080

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.

Other links and lift over

dbSNP: rs1238009086; hg19: chr2-87201283; COSMIC: COSV101233593; COSMIC: COSV101233593; API