Variant 2-107843660-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_182588.3(RGPD4):c.712G>A(p.Ala238Thr) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0091 ( 2 hom., cov: 3)

Exomes 𝑓: 0.027 ( 401 hom. )

Failed GnomAD Quality Control

Consequence

RGPD4
NM_182588.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.20

Variant links:

Genes affected

RGPD4 (HGNC:32417): (RANBP2 like and GRIP domain containing 4) 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]

RGPD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011023074).

BP6

Variant 2-107843660-G-A is Benign according to our data. Variant chr2-107843660-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2358969.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGPD4	NM_182588.3 linkuse as main transcript	c.712G>A	p.Ala238Thr	missense_variant	6/23	ENST00000408999.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGPD4	ENST00000408999.4 linkuse as main transcript	c.712G>A	p.Ala238Thr	missense_variant	6/23	1	NM_182588.3	P1	Q7Z3J3-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

149

AN:

16114

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00800

Gnomad ASJ

AF:

0.0220

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0148

Gnomad FIN

AF:

0.00266

Gnomad MID

AF:

0.0652

Gnomad NFE

AF:

0.0145

Gnomad OTH

AF:

0.0313

GnomAD3 exomes

AF:

0.0144

AC:

AN:

4388

Hom.:

AF XY:

0.0137

AC XY:

AN XY:

2266

show subpopulations

Gnomad AFR exome

AF:

0.00455

Gnomad AMR exome

AF:

0.0179

Gnomad ASJ exome

AF:

0.0139

Gnomad EAS exome

AF:

0.000710

Gnomad SAS exome

AF:

0.0520

Gnomad FIN exome

AF:

0.0208

Gnomad NFE exome

AF:

0.0127

Gnomad OTH exome

AF:

0.0410

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0269

AC:

6439

AN:

239690

Hom.:

401

Cov.:

AF XY:

0.0274

AC XY:

3458

AN XY:

126184

show subpopulations

Gnomad4 AFR exome

AF:

0.00667

Gnomad4 AMR exome

AF:

0.0168

Gnomad4 ASJ exome

AF:

0.0434

Gnomad4 EAS exome

AF:

0.000343

Gnomad4 SAS exome

AF:

0.0436

Gnomad4 FIN exome

AF:

0.0112

Gnomad4 NFE exome

AF:

0.0316

Gnomad4 OTH exome

AF:

0.0295

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00913

AC:

147

AN:

16108

Hom.:

Cov.:

AF XY:

0.00781

AC XY:

AN XY:

7428

show subpopulations

Gnomad4 AFR

AF:

0.00146

Gnomad4 AMR

AF:

0.00797

Gnomad4 ASJ

AF:

0.0220

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.0151

Gnomad4 FIN

AF:

0.00266

Gnomad4 NFE

AF:

0.0145

Gnomad4 OTH

AF:

0.0268

ExAC

AF:

0.000604

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.092

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.86

M_CAP

Benign

0.0066

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

0.85

N;N

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.22

Sift

Benign

0.033

Sift4G

Uncertain

0.018

Polyphen

0.98

Vest4

0.51

ClinPred

0.046

GERP RS

2.6

Varity_R

0.15

gMVP

0.030

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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