1-36089004-G-A

Position:

• chr1-36089004-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1 PM2 PP3_Strong PP5

The ENST00000373178.5(ADPRS):​c.100G>A​(p.Asp34Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D34G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADPRS ENST00000373178.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.19

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

• PM1: In a mutagenesis_site Reduces hydrolase activity. (size 0) in uniprot entity ADPRS_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.977
• PP5: Variant 1-36089004-G-A is Pathogenic according to our data. Variant chr1-36089004-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 590303.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADPRS	NM_017825.3	c.100G>A	p.Asp34Asn	missense_variant	1/6	ENST00000373178.5	NP_060295.1
ADPRS	XM_011541636.3	c.-266G>A		5_prime_UTR_variant	1/5		XP_011539938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADPRS	ENST00000373178.5	c.100G>A	p.Asp34Asn	missense_variant	1/6	1	NM_017825.3	ENSP00000362273	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.90	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.61	D
MutationAssessor	Pathogenic	4.0	H
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-4.5	D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.90		Gain of MoRF binding (P = 0.0675);
MVP		0.98
MPC		0.82
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.95
gMVP		0.87

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

LitVar

Other links and lift over

dbSNP: rs1557732234; hg19: chr1-36554605;