Genetic Variant RGPD1:p.Pro1298Thr (chr2-86986791-C-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001382344.1(RGPD1):c.3892C>A(p.Pro1298Thr) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., cov: 7)

Exomes 𝑓: 0.000044 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RGPD1
NM_001382344.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.74

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 -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.36931962).

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.3892C>A	p.Pro1298Thr	missense	Exon 20 of 23	NP_001369273.1	A0A286YES2
RGPD1	NM_001410915.1		c.3892C>A	p.Pro1298Thr	missense	Exon 20 of 23	NP_001397844.1	F8VYC4
RGPD1	NM_001024457.4		c.3868C>A	p.Pro1290Thr	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.3892C>A	p.Pro1298Thr	missense	Exon 20 of 23	ENSP00000492954.1	A0A286YES2
RGPD1	ENST00000398193.8	TSL:1	c.3892C>A	p.Pro1298Thr	missense	Exon 20 of 23	ENSP00000381253.3	F8VYC4
RGPD1	ENST00000428128.1	TSL:1	n.*1811C>A		non_coding_transcript_exon	Exon 7 of 10	ENSP00000402729.1	H7C1V8

Frequencies

GnomAD3 genomes

AF:

0.0000363

AC:

AN:

55106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000589

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000440

AC:

AN:

1364242

Hom.:

Cov.:

AF XY:

0.0000424

AC XY:

AN XY:

683324

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22600

American (AMR)

AF:

0.00

AC:

AN:

44134

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25530

East Asian (EAS)

AF:

0.00

AC:

AN:

38896

South Asian (SAS)

AF:

0.00

AC:

AN:

84384

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52780

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3938

European-Non Finnish (NFE)

AF:

0.0000570

AC:

AN:

1035484

Other (OTH)

AF:

0.0000177

AC:

AN:

56496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000363

AC:

AN:

55106

Hom.:

Cov.:

AF XY:

0.0000778

AC XY:

AN XY:

25718

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

7442

American (AMR)

AF:

0.00

AC:

AN:

4470

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1856

East Asian (EAS)

AF:

0.00

AC:

AN:

1944

South Asian (SAS)

AF:

0.00

AC:

AN:

1106

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3198

Middle Eastern (MID)

AF:

0.00

AC:

AN:

108

European-Non Finnish (NFE)

AF:

0.0000589

AC:

AN:

33964

Other (OTH)

AF:

0.00

AC:

AN:

536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.00

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

0.11

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

Eigen

Benign

0.15

Eigen_PC

Benign

0.080

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.022

MetaRNN

Benign

0.37

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.4

PhyloP100

7.7

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-5.5

REVEL

Benign

0.25

Sift

Benign

0.032

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.24

MutPred

0.13

Gain of MoRF binding (P = 0.05)

MVP

0.18

ClinPred

0.98

GERP RS

2.4

Varity_R

0.41

gMVP

0.036

Mutation Taster

=82/18

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over