Genetic Variant NM_017825.3:c.53G>A (chr1-36088957-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_017825.3(ADPRS):c.53G>A(p.Arg18His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000295 in 1,355,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R18L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000030 ( 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3768628).

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>A	p.Arg18His	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>A	p.Arg18His	missense	Exon 1 of 6	ENSP00000362273.4	Q9NX46
ADPRS	ENST00000896939.1		c.53G>A	p.Arg18His	missense	Exon 1 of 6	ENSP00000566998.1
ADPRS	ENST00000932449.1		c.53G>A	p.Arg18His	missense	Exon 1 of 6	ENSP00000602508.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000309

AC:

AN:

97074

AF XY:

0.0000369

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000534

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000282

Gnomad OTH exome

AF:

0.000338

GnomAD4 exome

AF:

0.00000295

AC:

AN:

1355020

Hom.:

Cov.:

AF XY:

0.00000449

AC XY:

AN XY:

667832

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

27670

American (AMR)

AF:

0.0000333

AC:

AN:

30008

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23070

East Asian (EAS)

AF:

0.00

AC:

AN:

33186

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:

0.00000281

AC:

AN:

1065778

Other (OTH)

AF:

0.00

AC:

AN:

56324

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.250

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.015

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.67

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.5

PhyloP100

0.94

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.82

REVEL

Benign

0.091

Sift

Benign

0.067

Sift4G

Benign

0.35

Polyphen

1.0

Vest4

0.41

MutPred

0.39

Loss of MoRF binding (P = 0.0049)

MVP

0.71

MPC

0.94

ClinPred

0.43

GERP RS

4.7

PromoterAI

0.028

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.30

gMVP

0.34

Mutation Taster

=85/15

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over