Variant 2-86986990-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001382344.1(RGPD1):c.4091G>A(p.Gly1364Asp) variant causes a missense 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: not found (cov: 17)

Exomes 𝑓: 0.0000027 ( 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: 1.57

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21926841).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD1	NM_001382344.1 linkuse as main transcript	c.4091G>A	p.Gly1364Asp	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.4091G>A	p.Gly1364Asp	missense_variant	20/23		NM_001382344.1	ENSP00000492954.1	A0A286YES2
RGPD1	ENST00000398193.8 linkuse as main transcript	c.4091G>A	p.Gly1364Asp	missense_variant	20/23	1		ENSP00000381253.3	F8VYC4
RGPD1	ENST00000428128.1 linkuse as main transcript	n.*2010G>A		non_coding_transcript_exon_variant	7/10	1		ENSP00000402729.1	H7C1V8
RGPD1	ENST00000428128.1 linkuse as main transcript	n.*2010G>A		3_prime_UTR_variant	7/10	1		ENSP00000402729.1	H7C1V8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000275

AC:

AN:

1454614

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723970

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000500

GnomAD4 genome

Cov.:

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

Jan 30, 2024

The c.4067G>A (p.G1356D) alteration is located in exon 20 (coding exon 20) of the RGPD1 gene. This alteration results from a G to A substitution at nucleotide position 4067, causing the glycine (G) at amino acid position 1356 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

Benign

0.27

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.053

T;.;T;.

Eigen

Benign

-0.048

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.74

T;T;.;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.22

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.;L;.

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.7

D;D;D;.

REVEL

Benign

0.073

Sift

Benign

0.29

T;T;T;.

Sift4G

Benign

0.18

T;T;T;.

Polyphen

0.99

.;D;.;.

Vest4

0.32

MutPred

0.48

.;Loss of MoRF binding (P = 0.0404);.;Loss of MoRF binding (P = 0.0404);

MVP

0.14

ClinPred

0.51

GERP RS

2.4

Varity_R

0.20

gMVP

0.0091

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over