Genetic Variant ADPRS:p.Arg18Pro (chr1-36088957-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017825.3(ADPRS):c.53G>C(p.Arg18Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000199 in 1,507,352 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R18L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

ADPRS
NM_017825.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.939

Publications

0 publications found

Variant links:

Genes affected

ADPRS (HGNC:21304): (ADP-ribosylserine hydrolase) This gene encodes a member of the ADP-ribosylglycohydrolase family. The encoded enzyme catalyzes the removal of ADP-ribose from ADP-ribosylated proteins. This enzyme localizes to the mitochondria, in addition to the nucleus and cytoplasm.[provided by RefSeq, Feb 2009]

ADPRS Gene-Disease associations (from GenCC):

neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ADPRS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017825.3. 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
	ADPRS	NM_017825.3	MANE Select	c.53G>C	p.Arg18Pro	missense	Exon 1 of 6	NP_060295.1	Q9NX46

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADPRS	ENST00000373178.5	TSL:1 MANE Select	c.53G>C	p.Arg18Pro	missense	Exon 1 of 6	ENSP00000362273.4	Q9NX46
ADPRS	ENST00000896939.1		c.53G>C	p.Arg18Pro	missense	Exon 1 of 6	ENSP00000566998.1
ADPRS	ENST00000932449.1		c.53G>C	p.Arg18Pro	missense	Exon 1 of 6	ENSP00000602508.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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

AF:

7.38e-7

AC:

AN:

1355022

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

667832

show subpopulations

African (AFR)

AF:

0.0000361

AC:

AN:

27670

American (AMR)

AF:

0.00

AC:

AN:

30008

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23070

East Asian (EAS)

AF:

0.00

AC:

AN:

33188

South Asian (SAS)

AF:

0.00

AC:

AN:

74736

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39752

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4496

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1065778

Other (OTH)

AF:

0.00

AC:

AN:

56324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41580

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.46

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.2

PhyloP100

0.94

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.070

REVEL

Benign

0.13

Sift

Benign

0.22

Sift4G

Benign

0.34

Polyphen

0.99

Vest4

0.49

MutPred

0.44

Loss of MoRF binding (P = 3e-04)

MVP

0.74

MPC

1.0

ClinPred

0.94

GERP RS

4.7

PromoterAI

-0.073

Neutral

(source)

Varity_R

0.72

gMVP

0.69

Mutation Taster

=66/34

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over