1-36088951-C-T

Variant names:

• chr1-36088951-C-T
• rs1045143850
• NM_017825.3:c.47C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017825.3(ADPRS):​c.47C>T​(p.Ala16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 1,512,450 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000066 (0 hom.)
• Consequence: ADPRS NM_017825.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.043337286).

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>T	p.Ala16Val	missense	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.47C>T	p.Ala16Val	missense	Exon 1 of 6	ENSP00000362273.4	Q9NX46
	ADPRS	ENST00000896939.1		c.47C>T	p.Ala16Val	missense	Exon 1 of 6	ENSP00000566998.1
	ADPRS	ENST00000932449.1		c.47C>T	p.Ala16Val	missense	Exon 1 of 6	ENSP00000602508.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000586 AC: 6 AN: 102404 AF XY: 0.0000174

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000254

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000316

GnomAD4 exome AF: 0.00000662 AC: 9 AN: 1360238 Hom.: 0 Cov.: 32 AF XY: 0.00000149 AC XY: 1 AN XY: 670868

African (AFR) AF: 0.00 AC: 0 AN: 27920

American (AMR) AF: 0.000226 AC: 7 AN: 30988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23520

East Asian (EAS) AF: 0.00 AC: 0 AN: 33304

South Asian (SAS) AF: 0.00 AC: 0 AN: 76228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4452

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1068198

Other (OTH) AF: 0.00 AC: 0 AN: 56544

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74360

African (AFR) AF: 0.0000241 AC: 1 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0082	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.10
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	1.1	N
REVEL	Benign	0.040
Sift	Benign	0.067	T
Sift4G	Benign	0.33	T
Polyphen		0.0010	B
Vest4		0.14
MutPred		0.24		Loss of disorder (P = 0.0537)
MVP		0.33
MPC		0.22
ClinPred		0.15	T
GERP RS		3.8
PromoterAI		-0.073	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.075
gMVP		0.39
Mutation Taster		=91/9	polymorphism

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: rs1045143850; hg19: chr1-36554552;