Variant 2-86987040-G-T 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_001382344.1(RGPD1):c.4141G>T(p.Asp1381Tyr) 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 0.014 ( 52 hom., cov: 17)

Exomes 𝑓: 0.015 ( 810 hom. )

Failed GnomAD Quality Control

Consequence

RGPD1
NM_001382344.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.46

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]

RGPD1 links:

RGPD1 (HGNC:):

RGPD1 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=0.005544722).

BP6

Variant 2-86987040-G-T is Benign according to our data. Variant chr2-86987040-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3153633.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD1	NM_001382344.1 linkuse as main transcript	c.4141G>T	p.Asp1381Tyr	missense_variant	20/23	ENST00000641458.2	NP_001369273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RGPD1	ENST00000641458.2 linkuse as main transcript	c.4141G>T	p.Asp1381Tyr	missense_variant	20/23		NM_001382344.1	ENSP00000492954.1	A0A286YES2
RGPD1	ENST00000398193.8 linkuse as main transcript	c.4141G>T	p.Asp1381Tyr	missense_variant	20/23	1		ENSP00000381253.3	F8VYC4
RGPD1	ENST00000428128.1 linkuse as main transcript	n.*2060G>T		non_coding_transcript_exon_variant	7/10	1		ENSP00000402729.1	H7C1V8
RGPD1	ENST00000428128.1 linkuse as main transcript	n.*2060G>T		3_prime_UTR_variant	7/10	1		ENSP00000402729.1	H7C1V8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1743

AN:

122058

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00304

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00624

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.124

Gnomad SAS

AF:

0.0683

Gnomad FIN

AF:

0.0236

Gnomad MID

AF:

0.00360

Gnomad NFE

AF:

0.00869

Gnomad OTH

AF:

0.00900

GnomAD3 exomes

AF:

0.0341

AC:

1115

AN:

32730

Hom.:

AF XY:

0.0358

AC XY:

595

AN XY:

16642

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00511

Gnomad ASJ exome

AF:

0.00105

Gnomad EAS exome

AF:

0.130

Gnomad SAS exome

AF:

0.0679

Gnomad FIN exome

AF:

0.0304

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.0252

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0154

AC:

22239

AN:

1440270

Hom.:

810

Cov.:

AF XY:

0.0169

AC XY:

12125

AN XY:

717850

show subpopulations

Gnomad4 AFR exome

AF:

0.00272

Gnomad4 AMR exome

AF:

0.00428

Gnomad4 ASJ exome

AF:

0.00472

Gnomad4 EAS exome

AF:

0.107

Gnomad4 SAS exome

AF:

0.0601

Gnomad4 FIN exome

AF:

0.0255

Gnomad4 NFE exome

AF:

0.00885

Gnomad4 OTH exome

AF:

0.0226

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0142

AC:

1740

AN:

122114

Hom.:

Cov.:

AF XY:

0.0167

AC XY:

979

AN XY:

58734

show subpopulations

Gnomad4 AFR

AF:

0.00304

Gnomad4 AMR

AF:

0.00623

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.124

Gnomad4 SAS

AF:

0.0681

Gnomad4 FIN

AF:

0.0236

Gnomad4 NFE

AF:

0.00869

Gnomad4 OTH

AF:

0.00891

Alfa

AF:

0.0101

Hom.:

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

Jul 06, 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

0.26

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;.;T;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.97

D;D;.;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.0055

T;T;T;T

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.8

M;.;M;.

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-5.4

D;D;D;.

REVEL

Benign

0.24

Sift

Uncertain

0.017

D;D;D;.

Sift4G

Uncertain

0.0060

D;D;D;.

Polyphen

1.0

.;D;.;.

Vest4

0.38

ClinPred

0.054

GERP RS

2.4

Varity_R

0.59

gMVP

0.018

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