Variant 2-86986926-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001382344.1(RGPD1):c.4027G>C(p.Glu1343Gln) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 17)

Exomes 𝑓: 0.000057 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RGPD1
NM_001382344.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.78

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD1	NM_001382344.1 linkuse as main transcript	c.4027G>C	p.Glu1343Gln	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.4027G>C	p.Glu1343Gln	missense_variant	20/23		NM_001382344.1	ENSP00000492954.1	A0A286YES2
RGPD1	ENST00000398193.8 linkuse as main transcript	c.4027G>C	p.Glu1343Gln	missense_variant	20/23	1		ENSP00000381253.3	F8VYC4
RGPD1	ENST00000428128.1 linkuse as main transcript	n.*1946G>C		non_coding_transcript_exon_variant	7/10	1		ENSP00000402729.1	H7C1V8
RGPD1	ENST00000428128.1 linkuse as main transcript	n.*1946G>C		3_prime_UTR_variant	7/10	1		ENSP00000402729.1	H7C1V8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

139912

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000571

AC:

AN:

1454548

Hom.:

Cov.:

AF XY:

0.0000746

AC XY:

AN XY:

723944

show subpopulations

Gnomad4 AFR exome

AF:

0.0000346

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.0000684

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000143

AC:

AN:

139912

Hom.:

Cov.:

AF XY:

0.0000146

AC XY:

AN XY:

68302

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000217

AC:

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 18, 2022

The c.4003G>C (p.E1335Q) alteration is located in exon 20 (coding exon 20) of the RGPD1 gene. This alteration results from a G to C substitution at nucleotide position 4003, causing the glutamic acid (E) at amino acid position 1335 to be replaced by a glutamine (Q). 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

0.58

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;.;T;.

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

D;D;.;D

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.47

T;T;T;T

MetaSVM

Uncertain

0.22

MutationAssessor

Pathogenic

4.0

H;.;H;.

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.4

N;N;N;.

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

D;D;D;.

Sift4G

Benign

0.095

T;T;T;.

Polyphen

1.0

.;D;.;.

Vest4

0.59

MVP

0.32

ClinPred

0.59

GERP RS

2.4

Varity_R

0.50

gMVP

0.042

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