NM_017825.3:c.15_29dupGATGGCGGCAGCGGC

Variant names:

• chr1-36088910-C-CGCAGCGGCGATGGCG
• rs748995403
• NM_017825.3:c.15_29dupGATGGCGGCAGCGGC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_017825.3(ADPRS):​c.15_29dupGATGGCGGCAGCGGC​(p.Ala10_Gly11insMetAlaAlaAlaAla) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,524,930 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: ADPRS NM_017825.3 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01
• 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 -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_017825.3

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.15_29dupGATGGCGGCAGCGGC	p.Ala10_Gly11insMetAlaAlaAlaAla	disruptive_inframe_insertion	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.15_29dupGATGGCGGCAGCGGC	p.Ala10_Gly11insMetAlaAlaAlaAla	disruptive_inframe_insertion	Exon 1 of 6	ENSP00000362273.4	Q9NX46
	ADPRS	ENST00000896939.1		c.15_29dupGATGGCGGCAGCGGC	p.Ala10_Gly11insMetAlaAlaAlaAla	disruptive_inframe_insertion	Exon 1 of 6	ENSP00000566998.1
	ADPRS	ENST00000932449.1		c.15_29dupGATGGCGGCAGCGGC	p.Ala10_Gly11insMetAlaAlaAlaAla	disruptive_inframe_insertion	Exon 1 of 6	ENSP00000602508.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000254 AC: 3 AN: 118088 AF XY: 0.0000305

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000424

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: 0.00

GnomAD4 exome AF: 0.0000153 AC: 21 AN: 1372714 Hom.: 0 Cov.: 32 AF XY: 0.0000133 AC XY: 9 AN XY: 677646

African (AFR) AF: 0.0000691 AC: 2 AN: 28954

American (AMR) AF: 0.0000860 AC: 3 AN: 34874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24544

East Asian (EAS) AF: 0.0000592 AC: 2 AN: 33776

South Asian (SAS) AF: 0.0000509 AC: 4 AN: 78656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36766

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4240

European-Non Finnish (NFE) AF: 0.00000838 AC: 9 AN: 1073744

Other (OTH) AF: 0.0000175 AC: 1 AN: 57160

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74362

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0
Mutation Taster		=78/22	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs748995403; hg19: chr1-36554511;