Genetic Variant RGPD3:p.Leu1744Arg (chr2-106413119-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001144013.2(RGPD3):c.5231T>G(p.Leu1744Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L1744P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RGPD3
NM_001144013.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.67

Publications

0 publications found

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:

ENSG00000291125 (HGNC:):

ENSG00000291125 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0836505).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144013.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGPD3	NM_001144013.2	MANE Select	c.5231T>G	p.Leu1744Arg	missense	Exon 22 of 23	NP_001137485.1	A6NKT7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RGPD3	ENST00000409886.4	TSL:1 MANE Select	c.5231T>G	p.Leu1744Arg	missense	Exon 22 of 23	ENSP00000386588.4	A6NKT7
RGPD3	ENST00000304514.11	TSL:2	c.5213T>G	p.Leu1738Arg	missense	Exon 22 of 23	ENSP00000303659.8	J3KNE0
ENSG00000291125	ENST00000779577.1		n.468+22099A>C		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000137

AC:

AN:

1456686

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724498

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33372

American (AMR)

AF:

0.00

AC:

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25882

East Asian (EAS)

AF:

0.00

AC:

AN:

38870

South Asian (SAS)

AF:

0.00

AC:

AN:

85720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4050

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110836

Other (OTH)

AF:

0.0000167

AC:

AN:

59982

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.0042

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.85

M_CAP

Benign

0.0013

MetaRNN

Benign

0.084

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.81

PhyloP100

5.7

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.29

REVEL

Benign

0.13

Sift

Uncertain

0.016

Sift4G

Uncertain

0.0080

Polyphen

0.0010

Vest4

0.41

MutPred

0.40

Gain of disorder (P = 0.0301)

MVP

0.055

ClinPred

0.31

GERP RS

1.1

Varity_R

0.13

gMVP

0.093

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over