dbSNP rs1045143850: ADPRS:p.Ala16Glu (chr1-36088951-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.47C>A(p.Ala16Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000735 in 1,360,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. A16G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

ADPRS
NM_017825.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.103

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=0.093607515).

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.47C>A	p.Ala16Glu	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.47C>A	p.Ala16Glu	missense	Exon 1 of 6	ENSP00000362273.4	Q9NX46
ADPRS	ENST00000896939.1		c.47C>A	p.Ala16Glu	missense	Exon 1 of 6	ENSP00000566998.1
ADPRS	ENST00000932449.1		c.47C>A	p.Ala16Glu	missense	Exon 1 of 6	ENSP00000602508.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.35e-7

AC:

AN:

1360240

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

670870

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27920

American (AMR)

AF:

0.00

AC:

AN:

30988

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23520

East Asian (EAS)

AF:

0.00

AC:

AN:

33306

South Asian (SAS)

AF:

0.00

AC:

AN:

76228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39084

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4452

European-Non Finnish (NFE)

AF:

9.36e-7

AC:

AN:

1068198

Other (OTH)

AF:

0.00

AC:

AN:

56544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

0.11

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0085

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.44

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.094

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

-0.10

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.17

REVEL

Benign

0.033

Sift

Benign

0.096

Sift4G

Benign

0.32

Polyphen

0.0060

Vest4

0.30

MutPred

0.30

Loss of MoRF binding (P = 0.0232)

MVP

0.34

MPC

0.26

ClinPred

0.72

GERP RS

3.8

PromoterAI

0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.13

gMVP

0.51

Mutation Taster

=87/13

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