Genetic Variant RGPD1:p.Val1308Ile (chr2-86986821-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001382344.1(RGPD1):c.3922G>A(p.Val1308Ile) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 9)

Exomes 𝑓: 0.000045 ( 8 hom. )

Failed GnomAD Quality Control

Consequence

RGPD1
NM_001382344.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.36

Publications

0 publications found

Variant links:

Genes affected

RGPD1 (HGNC:32414): (RANBP2 like and GRIP domain containing 1) 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]

RGPD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20283967).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382344.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RGPD1	NM_001382344.1	MANE Select	c.3922G>A	p.Val1308Ile	missense	Exon 20 of 23	NP_001369273.1	A0A286YES2
RGPD1	NM_001410915.1		c.3922G>A	p.Val1308Ile	missense	Exon 20 of 23	NP_001397844.1	F8VYC4
RGPD1	NM_001024457.4		c.3898G>A	p.Val1300Ile	missense	Exon 20 of 23	NP_001019628.3	P0DJD0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RGPD1	ENST00000641458.2	MANE Select	c.3922G>A	p.Val1308Ile	missense	Exon 20 of 23	ENSP00000492954.1	A0A286YES2
RGPD1	ENST00000398193.8	TSL:1	c.3922G>A	p.Val1308Ile	missense	Exon 20 of 23	ENSP00000381253.3	F8VYC4
RGPD1	ENST00000428128.1	TSL:1	n.*1841G>A		non_coding_transcript_exon	Exon 7 of 10	ENSP00000402729.1	H7C1V8

Frequencies

GnomAD3 genomes

AF:

0.000190

AC:

AN:

68458

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000173

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

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:

0.0000454

AC:

AN:

1388976

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

695136

show subpopulations

African (AFR)

AF:

0.00184

AC:

AN:

23432

American (AMR)

AF:

0.0000676

AC:

AN:

44364

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25756

East Asian (EAS)

AF:

0.00

AC:

AN:

39092

South Asian (SAS)

AF:

0.0000118

AC:

AN:

85026

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53004

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3982

European-Non Finnish (NFE)

AF:

0.00000757

AC:

AN:

1056924

Other (OTH)

AF:

0.000139

AC:

AN:

57396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000190

AC:

AN:

68518

Hom.:

Cov.:

AF XY:

0.000156

AC XY:

AN XY:

32106

show subpopulations

African (AFR)

AF:

0.00121

AC:

AN:

9888

American (AMR)

AF:

0.000172

AC:

AN:

5800

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2256

East Asian (EAS)

AF:

0.00

AC:

AN:

2264

South Asian (SAS)

AF:

0.00

AC:

AN:

1574

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3972

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

41312

Other (OTH)

AF:

0.00

AC:

AN:

752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000590

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.033

Eigen

Benign

0.17

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.82

M_CAP

Benign

0.0091

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.3

PhyloP100

5.4

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.69

REVEL

Benign

0.12

Sift

Benign

0.23

Sift4G

Benign

0.14

Polyphen

0.96

Vest4

0.13

MVP

0.076

ClinPred

0.52

GERP RS

2.4

Varity_R

0.045

gMVP

0.014

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over