Variant 2-112388533-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001164463.1(RGPD8):c.4412C>A(p.Ser1471Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., cov: 14)

Exomes 𝑓: 0.000088 ( 5 hom. )

Failed GnomAD Quality Control

Consequence

RGPD8
NM_001164463.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.763

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033119053).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD8	NM_001164463.1 linkuse as main transcript	c.4412C>A	p.Ser1471Tyr	missense_variant	20/23	ENST00000302558.8	NP_001157935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD8	ENST00000302558.8 linkuse as main transcript	c.4412C>A	p.Ser1471Tyr	missense_variant	20/23	1	NM_001164463.1	ENSP00000306637	P1
RGPD8	ENST00000409750.5 linkuse as main transcript	c.3992C>A	p.Ser1331Tyr	missense_variant	19/22	1		ENSP00000386511

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

112016

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000331

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000366

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000266

AC:

AN:

30050

Hom.:

AF XY:

0.000259

AC XY:

AN XY:

15462

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000152

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00165

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000964

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000879

AC:

125

AN:

1422176

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

708044

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:

0.00136

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000276

Gnomad4 OTH exome

AF:

0.0000845

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000178

AC:

AN:

112092

Hom.:

Cov.:

AF XY:

0.0000374

AC XY:

AN XY:

53434

show subpopulations

Gnomad4 AFR

AF:

0.0000330

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000367

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

Aug 08, 2023

The c.4412C>A (p.S1471Y) alteration is located in exon 20 (coding exon 20) of the RGPD8 gene. This alteration results from a C to A substitution at nucleotide position 4412, causing the serine (S) at amino acid position 1471 to be replaced by a tyrosine (Y). 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

0.078

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.068

T;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.22

T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.029

Sift

Benign

0.057

T;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.18

B;.

Vest4

0.17

MutPred

0.33

Loss of disorder (P = 0.0027);.;

MVP

0.055

ClinPred

0.054

GERP RS

-3.2

Varity_R

0.21

gMVP

0.013

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