Variant chr2-107859114-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_182588.3(RGPD4):c.1277G>A(p.Gly426Asp) variant causes a missense, splice region change. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000064 ( 0 hom., cov: 10)

Exomes 𝑓: 0.000025 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RGPD4
NM_182588.3 missense, splice_region

Scores

Splicing: ADA: 0.01906

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.08

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGPD4	NM_182588.3 linkuse as main transcript	c.1277G>A	p.Gly426Asp	missense_variant, splice_region_variant	10/23	ENST00000408999.4
LOC124906057	XR_007087170.1 linkuse as main transcript	n.217-10481C>T		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.1277G>A	p.Gly426Asp	missense_variant, splice_region_variant	10/23	1	NM_182588.3	P1	Q7Z3J3-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

78576

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 MID

AF:

0.00

Gnomad NFE

AF:

0.000117

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000223

AC:

AN:

44764

Hom.:

AF XY:

0.0000436

AC XY:

AN XY:

22938

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000145

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000248

AC:

AN:

1046978

Hom.:

Cov.:

AF XY:

0.0000231

AC XY:

AN XY:

520006

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000296

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000286

Gnomad4 OTH exome

AF:

0.0000442

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000636

AC:

AN:

78576

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34814

show subpopulations

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:

0.000117

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

Apr 26, 2023

The c.1277G>A (p.G426D) alteration is located in exon 10 (coding exon 10) of the RGPD4 gene. This alteration results from a G to A substitution at nucleotide position 1277, causing the glycine (G) at amino acid position 426 to be replaced by an aspartic acid (D). 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

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.092

Eigen

Uncertain

0.31

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.86

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.73

MetaSVM

Uncertain

0.33

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

0.98

D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-4.1

REVEL

Uncertain

0.58

Sift

Benign

0.044

Sift4G

Uncertain

0.029

Polyphen

1.0

Vest4

0.69

MutPred

0.36

Loss of methylation at R429 (P = 0.057);

MVP

0.32

ClinPred

0.55

GERP RS

2.6

Varity_R

0.37

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.019

dbscSNV1_RF

Benign

0.25

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