Variant 2-106423289-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001144013.2(RGPD3):c.4678T>C(p.Phe1560Leu) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RGPD3
NM_001144013.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

Variant links:

Genes affected

RGPD3 (HGNC:32416): (RANBP2 like and GRIP domain containing 3) This gene is located in a cluster of Ran-binding protein related genes on chromosome 2 which arose through duplication in primates. The encoded protein contains an N-terminal TPR (tetratricopeptide repeat) domain, two Ran-binding domains, and a C-terminal GRIP domain (golgin-97, RanBP2alpha, Imh1p and p230/golgin-245) domain. [provided by RefSeq, Sep 2011]

RGPD3 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
RGPD3	NM_001144013.2 linkuse as main transcript	c.4678T>C	p.Phe1560Leu	missense_variant	20/23	ENST00000409886.4	NP_001137485.1
RGPD3	XM_017004738.2 linkuse as main transcript	c.4702T>C	p.Phe1568Leu	missense_variant	21/24		XP_016860227.1
RGPD3	XM_047445567.1 linkuse as main transcript	c.4702T>C	p.Phe1568Leu	missense_variant	21/22		XP_047301523.1
RGPD3	XM_017004739.3 linkuse as main transcript	c.4702T>C	p.Phe1568Leu	missense_variant	21/22		XP_016860228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD3	ENST00000409886.4 linkuse as main transcript	c.4678T>C	p.Phe1560Leu	missense_variant	20/23	1	NM_001144013.2	ENSP00000386588	P2
RGPD3	ENST00000304514.11 linkuse as main transcript	c.4660T>C	p.Phe1554Leu	missense_variant	20/23	2		ENSP00000303659	A2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152248

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:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

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:

0.00000343

AC:

AN:

1459600

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726108

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000131

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.000207

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

Mar 21, 2022

The c.4678T>C (p.F1560L) alteration is located in exon 20 (coding exon 20) of the RGPD3 gene. This alteration results from a T to C substitution at nucleotide position 4678, causing the phenylalanine (F) at amino acid position 1560 to be replaced by a leucine (L). 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

0.91

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

.;T

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.088

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.0089

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.3

.;M

MutationTaster

Benign

0.99

N;N

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-3.2

.;D

REVEL

Benign

0.17

Sift

Uncertain

0.019

.;D

Sift4G

Benign

0.47

T;T

Polyphen

0.091

.;B

Vest4

0.64

MutPred

0.35

.;Loss of methylation at K1556 (P = 0.1095);

MVP

0.11

ClinPred

0.35

GERP RS

2.4

Varity_R

0.20

gMVP

0.019

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