chr1-36089049-AC-A

Variant names:

• chr1-36089049-AC-A
• NM_017825.3:c.146delC

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_017825.3(ADPRS):​c.146delC​(p.Thr49SerfsTer42) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADPRS NM_017825.3 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.03
• Publications: 0 publications found

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

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-36089049-AC-A is Pathogenic according to our data. Variant chr1-36089049-AC-A is described in ClinVar as Pathogenic. ClinVar VariationId is 2572385.Status of the report is criteria_provided_single_submitter, 1 stars.

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.146delC	p.Thr49SerfsTer42	frameshift	Exon 1 of 6	NP_060295.1	Q9NX46

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADPRS	ENST00000373178.5	TSL:1 MANE Select	c.146delC	p.Thr49SerfsTer42	frameshift	Exon 1 of 6	ENSP00000362273.4	Q9NX46
	ADPRS	ENST00000896939.1		c.146delC	p.Thr49SerfsTer41	frameshift	Exon 1 of 6	ENSP00000566998.1
	ADPRS	ENST00000932449.1		c.146delC	p.Thr49SerfsTer38	frameshift	Exon 1 of 6	ENSP00000602508.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.24		Position offset: 0

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

Other links and lift over

hg19: chr1-36554650;