2-112388348-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001164463.1(RGPD8):​c.4597G>A​(p.Val1533Ile) 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 0.000010 ( 0 hom., cov: 13)
Exomes 𝑓: 0.0000057 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RGPD8
NM_001164463.1 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.59
Variant links:
Genes affected
RGPD8 (HGNC:9849): (RANBP2 like and GRIP domain containing 8) 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 -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.18782023).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RGPD8NM_001164463.1 linkc.4597G>A p.Val1533Ile missense_variant Exon 20 of 23 ENST00000302558.8 NP_001157935.1 O14715

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RGPD8ENST00000302558.8 linkc.4597G>A p.Val1533Ile missense_variant Exon 20 of 23 1 NM_001164463.1 ENSP00000306637.3 O14715
RGPD8ENST00000409750.5 linkc.4177G>A p.Val1393Ile missense_variant Exon 19 of 22 1 ENSP00000386511.1 J3KQ37

Frequencies

GnomAD3 genomes
AF:
0.0000102
AC:
1
AN:
98366
Hom.:
0
Cov.:
13
show subpopulations
Gnomad AFR
AF:
0.0000416
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000573
AC:
8
AN:
1397282
Hom.:
0
Cov.:
33
AF XY:
0.00000574
AC XY:
4
AN XY:
696560
show subpopulations
Gnomad4 AFR exome
AF:
0.0000633
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000564
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000102
AC:
1
AN:
98366
Hom.:
0
Cov.:
13
AF XY:
0.00
AC XY:
0
AN XY:
46388
show subpopulations
Gnomad4 AFR
AF:
0.0000416
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:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 18, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.4597G>A (p.V1533I) alteration is located in exon 20 (coding exon 20) of the RGPD8 gene. This alteration results from a G to A substitution at nucleotide position 4597, causing the valine (V) at amino acid position 1533 to be replaced by an isoleucine (I). 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
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.014
T;T
Eigen
Uncertain
0.32
Eigen_PC
Benign
0.19
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-0.66
T
MutationAssessor
Uncertain
2.7
M;.
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-0.64
N;N
REVEL
Benign
0.12
Sift
Benign
0.088
T;D
Sift4G
Uncertain
0.013
D;D
Polyphen
1.0
D;.
Vest4
0.25
MVP
0.048
ClinPred
0.70
D
GERP RS
2.3
Varity_R
0.080
gMVP
0.015

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: rs1204358571; hg19: chr2-113145925; API