Variant 2-112378247-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001164463.1(RGPD8):c.5069A>G(p.Lys1690Arg) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.015 ( 0 hom., cov: 0)

Exomes 𝑓: 0.021 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

RGPD8
NM_001164463.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.89

Variant links:

Genes affected

RGPD8 (HGNC:9849): (RANBP2 like and GRIP domain containing 8) 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]

RGPD8 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
RGPD8	NM_001164463.1 linkuse as main transcript	c.5069A>G	p.Lys1690Arg	missense_variant	22/23	ENST00000302558.8	NP_001157935.1
RGPD8	XM_024453101.2 linkuse as main transcript	c.4991A>G	p.Lys1664Arg	missense_variant	22/23		XP_024308869.1
RGPD8	XM_047445676.1 linkuse as main transcript	c.4214A>G	p.Lys1405Arg	missense_variant	17/18		XP_047301632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD8	ENST00000302558.8 linkuse as main transcript	c.5069A>G	p.Lys1690Arg	missense_variant	22/23	1	NM_001164463.1	ENSP00000306637	P1
RGPD8	ENST00000409750.5 linkuse as main transcript	c.4649A>G	p.Lys1550Arg	missense_variant	21/22	1		ENSP00000386511

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

124

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMR

AF:

0.0625

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0385

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: AS_VQSR

AF:

0.0209

AC:

1650

AN:

78866

Hom.:

Cov.:

AF XY:

0.0220

AC XY:

919

AN XY:

41698

show subpopulations

Gnomad4 AFR exome

AF:

0.00371

Gnomad4 AMR exome

AF:

0.0644

Gnomad4 ASJ exome

AF:

0.0313

Gnomad4 EAS exome

AF:

0.0593

Gnomad4 SAS exome

AF:

0.0399

Gnomad4 FIN exome

AF:

0.0116

Gnomad4 NFE exome

AF:

0.0103

Gnomad4 OTH exome

AF:

0.0211

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0154

AC:

AN:

130

Hom.:

Cov.:

AF XY:

0.0167

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0625

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00632

Hom.:

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 07, 2022

The c.5069A>G (p.K1690R) alteration is located in exon 22 (coding exon 22) of the RGPD8 gene. This alteration results from a A to G substitution at nucleotide position 5069, causing the lysine (K) at amino acid position 1690 to be replaced by an arginine (R). 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

0.096

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0046

T;T

Eigen

Benign

0.027

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.0037

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

0.99

N;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.21

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.034

D;D

Polyphen

0.98

D;.

Vest4

0.14

MutPred

0.23

Gain of MoRF binding (P = 0.0798);.;

MVP

0.030

ClinPred

0.85

GERP RS

0.86

Varity_R

0.23

gMVP

0.062

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: -1

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