Genetic Variant NM_017825.3:c.32G>T (chr1-36088936-G-T) – 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.32G>T(p.Gly11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,372,476 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. G11D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

ADPRS
NM_017825.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.659

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.089508146).

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.32G>T	p.Gly11Val	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.32G>T	p.Gly11Val	missense	Exon 1 of 6	ENSP00000362273.4	Q9NX46
ADPRS	ENST00000896939.1		c.32G>T	p.Gly11Val	missense	Exon 1 of 6	ENSP00000566998.1
ADPRS	ENST00000932449.1		c.32G>T	p.Gly11Val	missense	Exon 1 of 6	ENSP00000602508.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000146

AC:

AN:

1372476

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

677326

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28804

American (AMR)

AF:

0.00

AC:

AN:

34146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24416

East Asian (EAS)

AF:

0.00

AC:

AN:

33782

South Asian (SAS)

AF:

0.00

AC:

AN:

78408

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38200

Middle Eastern (MID)

AF:

0.000218

AC:

AN:

4578

European-Non Finnish (NFE)

AF:

9.32e-7

AC:

AN:

1073040

Other (OTH)

AF:

0.00

AC:

AN:

57102

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

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

Benign

0.18

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.0066

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.32

M_CAP

Benign

0.043

MetaRNN

Benign

0.090

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

0.66

PrimateAI

Uncertain

0.74

PROVEAN

Benign

0.40

REVEL

Benign

0.041

Sift

Benign

0.13

Sift4G

Benign

0.27

Polyphen

0.0050

Vest4

0.28

MutPred

0.30

Loss of disorder (P = 0.0896)

MVP

0.54

MPC

0.28

ClinPred

0.070

GERP RS

1.4

PromoterAI

0.025

Neutral

(source)

Varity_R

0.030

gMVP

0.54

Mutation Taster

=93/7

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