Variant chr2-112380948-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000302558.8(RGPD8):c.4937A>G(p.His1646Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 16)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

RGPD8
ENST00000302558.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.60

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07189283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD8	NM_001164463.1 linkuse as main transcript	c.4937A>G	p.His1646Arg	missense_variant	21/23	ENST00000302558.8	NP_001157935.1	O14715
RGPD8	XM_024453101.2 linkuse as main transcript	c.4859A>G	p.His1620Arg	missense_variant	21/23		XP_024308869.1
RGPD8	XM_047445676.1 linkuse as main transcript	c.4082A>G	p.His1361Arg	missense_variant	16/18		XP_047301632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD8	ENST00000302558.8 linkuse as main transcript	c.4937A>G	p.His1646Arg	missense_variant	21/23	1	NM_001164463.1	ENSP00000306637.3		O14715
RGPD8	ENST00000409750.5 linkuse as main transcript	c.4517A>G	p.His1506Arg	missense_variant	20/22	1		ENSP00000386511.1		J3KQ37

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000637

AC:

AN:

157096

Hom.:

AF XY:

0.0000119

AC XY:

AN XY:

84134

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000148

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000840

AC:

AN:

952036

Hom.:

Cov.:

AF XY:

0.00000619

AC XY:

AN XY:

484824

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:

0.0000118

Gnomad4 OTH exome

AF:

0.00

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

Sep 14, 2023

The c.4937A>G (p.H1646R) alteration is located in exon 21 (coding exon 21) of the RGPD8 gene. This alteration results from a A to G substitution at nucleotide position 4937, causing the histidine (H) at amino acid position 1646 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

0.079

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.0039

T;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.072

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.32

N;N

REVEL

Benign

0.031

Sift

Uncertain

0.011

D;D

Sift4G

Uncertain

0.023

D;D

Polyphen

0.063

B;.

Vest4

0.15

MutPred

0.28

Loss of helix (P = 0.0093);.;

MVP

0.014

ClinPred

0.10

GERP RS

0.72

Varity_R

0.11

gMVP

0.012

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