Variant 2-112388229-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000302558.8(RGPD8):c.4716T>G(p.Ser1572Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 15)

Exomes 𝑓: 0.000027 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RGPD8
ENST00000302558.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

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]

RGPD8 links:

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=0.121480465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD8	NM_001164463.1 linkuse as main transcript	c.4716T>G	p.Ser1572Arg	missense_variant	20/23	ENST00000302558.8	NP_001157935.1	O14715

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD8	ENST00000302558.8 linkuse as main transcript	c.4716T>G	p.Ser1572Arg	missense_variant	20/23	1	NM_001164463.1	ENSP00000306637.3		O14715
RGPD8	ENST00000409750.5 linkuse as main transcript	c.4296T>G	p.Ser1432Arg	missense_variant	19/22	1		ENSP00000386511.1		J3KQ37

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

118296

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000467

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000175

Gnomad OTH

AF:

0.000663

GnomAD3 exomes

AF:

0.0000704

AC:

AN:

42590

Hom.:

AF XY:

0.000137

AC XY:

AN XY:

21966

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000323

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000629

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000271

AC:

AN:

1403602

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

699064

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000763

Gnomad4 SAS exome

AF:

0.000230

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000140

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000338

AC:

AN:

118370

Hom.:

Cov.:

AF XY:

0.0000534

AC XY:

AN XY:

56154

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000468

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000175

Gnomad4 OTH

AF:

0.000654

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 28, 2023

The c.4716T>G (p.S1572R) alteration is located in exon 20 (coding exon 20) of the RGPD8 gene. This alteration results from a T to G substitution at nucleotide position 4716, causing the serine (S) at amino acid position 1572 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

Pathogenic

0.90

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.092

T;T

Eigen

Benign

-0.056

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.0087

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

0.50

D;N

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.13

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.91

P;.

Vest4

0.22

MutPred

0.32

Gain of methylation at S1572 (P = 0.014);.;

MVP

0.12

ClinPred

0.20

GERP RS

1.1

Varity_R

0.24

gMVP

0.045

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