rs768000

Variant names:

• chr1-36091266-C-T
• rs768000
• NM_017825.3:c.234C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_017825.3(ADPRS):​c.234C>T​(p.Asp78Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,614,118 control chromosomes in the GnomAD database, including 1,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.031 (241 hom., cov: 33)
  • Exomes 𝑓: 0.012 (1118 hom.)
• Consequence: ADPRS NM_017825.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.11
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 1-36091266-C-T is Benign according to our data. Variant chr1-36091266-C-T is described in ClinVar as Benign. ClinVar VariationId is 3058872.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=3.11 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

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.234C>T	p.Asp78Asp	synonymous	Exon 2 of 6	NP_060295.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADPRS	ENST00000373178.5	TSL:1 MANE Select	c.234C>T	p.Asp78Asp	synonymous	Exon 2 of 6	ENSP00000362273.4
	ADPRS	ENST00000896939.1		c.231C>T	p.Asp77Asp	synonymous	Exon 2 of 6	ENSP00000566998.1
	ADPRS	ENST00000932449.1		c.222C>T	p.Asp74Asp	synonymous	Exon 2 of 6	ENSP00000602508.1

Frequencies

GnomAD3 genomes AF: 0.0305 AC: 4636 AN: 152198 Hom.: 241 Cov.: 33

Gnomad AFR AF: 0.0574

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0334

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0267

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00194

Gnomad OTH AF: 0.0253

GnomAD2 exomes AF: 0.0327 AC: 8222 AN: 251226 AF XY: 0.0284

Gnomad AFR exome AF: 0.0606

Gnomad AMR exome AF: 0.0454

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.240

Gnomad FIN exome AF: 0.0301

Gnomad NFE exome AF: 0.00247

Gnomad OTH exome AF: 0.0213

GnomAD4 exome AF: 0.0116 AC: 16984 AN: 1461802 Hom.: 1118 Cov.: 31 AF XY: 0.0111 AC XY: 8038 AN XY: 727206

African (AFR) AF: 0.0565 AC: 1891 AN: 33476

American (AMR) AF: 0.0457 AC: 2043 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26136

East Asian (EAS) AF: 0.206 AC: 8192 AN: 39686

South Asian (SAS) AF: 0.00781 AC: 674 AN: 86256

European-Finnish (FIN) AF: 0.0272 AC: 1450 AN: 53396

Middle Eastern (MID) AF: 0.00746 AC: 43 AN: 5766

European-Non Finnish (NFE) AF: 0.00114 AC: 1264 AN: 1111986

Other (OTH) AF: 0.0235 AC: 1418 AN: 60382

GnomAD4 genome AF: 0.0305 AC: 4646 AN: 152316 Hom.: 241 Cov.: 33 AF XY: 0.0323 AC XY: 2405 AN XY: 74484

African (AFR) AF: 0.0574 AC: 2387 AN: 41554

American (AMR) AF: 0.0339 AC: 519 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.234 AC: 1212 AN: 5186

South Asian (SAS) AF: 0.0118 AC: 57 AN: 4826

European-Finnish (FIN) AF: 0.0267 AC: 284 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00193 AC: 131 AN: 68034

Other (OTH) AF: 0.0251 AC: 53 AN: 2114

Alfa AF: 0.0107 Hom.: 93

Bravo AF: 0.0339

Asia WGS AF: 0.102 AC: 352 AN: 3478

EpiCase AF: 0.00104

EpiControl AF: 0.00196

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ADPRS-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		3.1
Mutation Taster		=41/59	polymorphism (auto)

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

Other links and lift over

dbSNP: rs768000; hg19: chr1-36556867; COSMIC: COSV52881466; COSMIC: COSV52881466;