1-36091270-G-T

Position:

• chr1-36091270-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017825.3(ADPRS):​c.238G>T​(p.Ala80Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADPRS NM_017825.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.68

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADPRS	NM_017825.3	c.238G>T	p.Ala80Ser	missense_variant	2/6	ENST00000373178.5	NP_060295.1
ADPRS	XM_011541636.3	c.-154-348G>T		intron_variant			XP_011539938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADPRS	ENST00000373178.5	c.238G>T	p.Ala80Ser	missense_variant	2/6	1	NM_017825.3	ENSP00000362273	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Mar 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.45		Gain of disorder (P = 0.0485);
MVP		0.46
MPC		0.80
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.95
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-36556871;