Variant chr2-86985576-G-T 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.2677G>T(p.Gly893Cys) variant causes a missense, splice region 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 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RGPD1
NM_001382344.1 missense, splice_region

Scores

Splicing: ADA: 0.8728

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.102

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:

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.2677G>T	p.Gly893Cys	missense_variant, splice_region_variant	20/23	ENST00000641458.2	NP_001369273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RGPD1	ENST00000641458.2 linkuse as main transcript	c.2677G>T	p.Gly893Cys	missense_variant, splice_region_variant	20/23		NM_001382344.1	ENSP00000492954	A2
RGPD1	ENST00000398193.8 linkuse as main transcript	c.2677G>T	p.Gly893Cys	missense_variant, splice_region_variant	20/23	1		ENSP00000381253	P4
RGPD1	ENST00000428128.1 linkuse as main transcript	c.*596G>T		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	7/10	1		ENSP00000402729

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

6316

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

38478

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

19764

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

6324

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

3074

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Jul 05, 2023

The c.2653G>T (p.G885C) alteration is located in exon 20 (coding exon 20) of the RGPD1 gene. This alteration results from a G to T substitution at nucleotide position 2653, causing the glycine (G) at amino acid position 885 to be replaced by a cysteine (C). 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

Benign

0.12

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;.;T;.

Eigen

Benign

-0.074

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.46

T;T;.;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.1

M;.;M;.

MutationTaster

Benign

0.85

D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.0

D;D;D;.

REVEL

Benign

0.072

Sift

Uncertain

0.0070

D;D;D;.

Sift4G

Uncertain

0.014

D;D;D;.

Polyphen

0.98

.;D;.;.

Vest4

0.25

MutPred

0.42

.;Loss of glycosylation at T891 (P = 0.0374);.;Loss of glycosylation at T891 (P = 0.0374);

MVP

0.25

ClinPred

0.93

GERP RS

1.4

Varity_R

0.26

gMVP

0.028

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.87

dbscSNV1_RF

Pathogenic

0.72

SpliceAI score (max)

0.38

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.38

Position offset: 16

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