Genetic Variant ADPRS:p.Ala8Glu (chr1-36088927-C-A) – 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_017825.3(ADPRS):c.23C>A(p.Ala8Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. A8V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ADPRS
NM_017825.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.709

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18669659).

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.23C>A	p.Ala8Glu	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.23C>A	p.Ala8Glu	missense	Exon 1 of 6	ENSP00000362273.4	Q9NX46
ADPRS	ENST00000896939.1		c.23C>A	p.Ala8Glu	missense	Exon 1 of 6	ENSP00000566998.1
ADPRS	ENST00000932449.1		c.23C>A	p.Ala8Glu	missense	Exon 1 of 6	ENSP00000602508.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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: AC0

AF:

0.00

AC:

AN:

1373664

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

677942

African (AFR)

AF:

0.00

AC:

AN:

28896

American (AMR)

AF:

0.00

AC:

AN:

34566

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24480

East Asian (EAS)

AF:

0.00

AC:

AN:

33796

South Asian (SAS)

AF:

0.00

AC:

AN:

78582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4452

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1073528

Other (OTH)

AF:

0.00

AC:

AN:

57146

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2088

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

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.018

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.37

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

0.71

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.42

REVEL

Benign

0.18

Sift

Benign

0.037

Sift4G

Uncertain

0.027

Polyphen

0.86

Vest4

0.30

MutPred

0.21

Loss of MoRF binding (P = 0.0814)

MVP

0.29

MPC

0.26

ClinPred

0.49

GERP RS

2.4

PromoterAI

0.11

Neutral

(source)

Varity_R

0.13

gMVP

0.59

Mutation Taster

=89/11

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over