Variant 2-107859153-C-G 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.1316C>G(p.Thr439Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0088 ( 3 hom., cov: 10)

Exomes 𝑓: 0.014 ( 127 hom. )

Failed GnomAD Quality Control

Consequence

RGPD4
NM_182588.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.47

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:

LOC124906057 (HGNC:):

LOC124906057 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=0.010481805).

BP6

Variant 2-107859153-C-G is Benign according to our data. Variant chr2-107859153-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2343180.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.1316C>G	p.Thr439Ser	missense_variant	10/23	ENST00000408999.4
LOC124906057	XR_007087170.1 linkuse as main transcript	n.217-10520G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGPD4	ENST00000408999.4 linkuse as main transcript	c.1316C>G	p.Thr439Ser	missense_variant	10/23	1	NM_182588.3	P1	Q7Z3J3-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

768

AN:

87026

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00201

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00657

Gnomad ASJ

AF:

0.00585

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000915

Gnomad FIN

AF:

0.00851

Gnomad MID

AF:

0.0111

Gnomad NFE

AF:

0.0132

Gnomad OTH

AF:

0.00869

GnomAD3 exomes

AF:

0.00855

AC:

454

AN:

53096

Hom.:

AF XY:

0.00936

AC XY:

251

AN XY:

26812

show subpopulations

Gnomad AFR exome

AF:

0.00235

Gnomad AMR exome

AF:

0.00645

Gnomad ASJ exome

AF:

0.00616

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00482

Gnomad FIN exome

AF:

0.0102

Gnomad NFE exome

AF:

0.0156

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0141

AC:

13266

AN:

941456

Hom.:

127

Cov.:

AF XY:

0.0137

AC XY:

6449

AN XY:

472314

show subpopulations

Gnomad4 AFR exome

AF:

0.00243

Gnomad4 AMR exome

AF:

0.00569

Gnomad4 ASJ exome

AF:

0.00653

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00379

Gnomad4 FIN exome

AF:

0.0104

Gnomad4 NFE exome

AF:

0.0167

Gnomad4 OTH exome

AF:

0.0121

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00883

AC:

769

AN:

87078

Hom.:

Cov.:

AF XY:

0.00765

AC XY:

300

AN XY:

39210

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00656

Gnomad4 ASJ

AF:

0.00585

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00138

Gnomad4 FIN

AF:

0.00851

Gnomad4 NFE

AF:

0.0132

Gnomad4 OTH

AF:

0.00856

Alfa

AF:

0.00984

Hom.:

Bravo

AF:

0.00926

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

Apr 25, 2022

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

0.23

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.013

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.83

M_CAP

Benign

0.0035

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-2.1

REVEL

Benign

0.051

Sift

Benign

0.14

Sift4G

Uncertain

0.010

Polyphen

0.028

Vest4

0.16

MutPred

0.26

Gain of helix (P = 0.0425);

MVP

0.11

ClinPred

0.014

GERP RS

2.6

Varity_R

0.14

gMVP

0.070

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