Genetic Variant RGPD1:p.Asn1243Lys (chr2-86986628-C-G) – 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.3729C>G(p.Asn1243Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 4)

Exomes 𝑓: 0.000038 ( 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: 0.634

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=0.20208523).

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.3729C>G	p.Asn1243Lys	missense	Exon 20 of 23	NP_001369273.1	A0A286YES2
RGPD1	NM_001410915.1		c.3729C>G	p.Asn1243Lys	missense	Exon 20 of 23	NP_001397844.1	F8VYC4
RGPD1	NM_001024457.4		c.3705C>G	p.Asn1235Lys	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.3729C>G	p.Asn1243Lys	missense	Exon 20 of 23	ENSP00000492954.1	A0A286YES2
RGPD1	ENST00000398193.8	TSL:1	c.3729C>G	p.Asn1243Lys	missense	Exon 20 of 23	ENSP00000381253.3	F8VYC4
RGPD1	ENST00000428128.1	TSL:1	n.*1648C>G		non_coding_transcript_exon	Exon 7 of 10	ENSP00000402729.1	H7C1V8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

10810

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000385

AC:

AN:

468100

Hom.:

Cov.:

AF XY:

0.0000365

AC XY:

AN XY:

246734

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

10338

American (AMR)

AF:

0.00

AC:

AN:

21062

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14250

East Asian (EAS)

AF:

0.00

AC:

AN:

30332

South Asian (SAS)

AF:

0.00

AC:

AN:

46690

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31484

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1998

European-Non Finnish (NFE)

AF:

0.0000630

AC:

AN:

285576

Other (OTH)

AF:

0.00

AC:

AN:

26370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

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: AC0;AS_VQSR

AF:

0.00

AC:

AN:

10810

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

4894

African (AFR)

AF:

0.00

AC:

AN:

1420

American (AMR)

AF:

0.00

AC:

AN:

1060

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

262

East Asian (EAS)

AF:

0.00

AC:

AN:

608

South Asian (SAS)

AF:

0.00

AC:

AN:

430

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

5390

Other (OTH)

AF:

0.00

AC:

AN:

164

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

0.26

PhyloP100

0.63

Varity_R

0.25

gMVP

0.025

Mutation Taster

=92/8

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over