chr10-49832811-C-T

Variant names:

• chr10-49832811-C-T
• NM_003631.5:c.2639G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003631.5(PARG):​c.2639G>A​(p.Arg880Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PARG NM_003631.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.67
• Publications: 0 publications found

Genes affected

PARG (HGNC:8605): (poly(ADP-ribose) glycohydrolase) Poly(ADP-ribose) glycohydrolase (PARG) is the major enzyme responsible for the catabolism of poly(ADP-ribose), a reversible covalent-modifier of chromosomal proteins. The protein is found in many tissues and may be subject to proteolysis generating smaller, active products. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33311135).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003631.5. 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
	PARG	NM_003631.5	MANE Select	c.2639G>A	p.Arg880Lys	missense	Exon 16 of 18	NP_003622.2	Q86W56-1
	PARG	NM_001303486.3		c.2393G>A	p.Arg798Lys	missense	Exon 16 of 18	NP_001290415.1	Q86W56-2
	PARG	NM_001324381.3		c.2393G>A	p.Arg798Lys	missense	Exon 16 of 18	NP_001311310.1	Q86W56-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARG	ENST00000616448.2	TSL:1 MANE Select	c.2639G>A	p.Arg880Lys	missense	Exon 16 of 18	ENSP00000484285.1	Q86W56-1
	PARG	ENST00000402038.7	TSL:1	c.2639G>A	p.Arg880Lys	missense	Exon 17 of 19	ENSP00000384408.3	Q86W56-1
	PARG	ENST00000941174.1		c.2639G>A	p.Arg880Lys	missense	Exon 16 of 18	ENSP00000611233.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1383578 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 683520

African (AFR) AF: 0.00 AC: 0 AN: 31116

American (AMR) AF: 0.00 AC: 0 AN: 35188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25012

East Asian (EAS) AF: 0.00 AC: 0 AN: 35586

South Asian (SAS) AF: 0.00 AC: 0 AN: 78570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1065848

Other (OTH) AF: 0.00 AC: 0 AN: 57368

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.7
PrimateAI	Uncertain	0.73	T
REVEL	Benign	0.16
Sift4G	Benign	0.18	T
Polyphen		0.62	P
Vest4		0.38
MutPred		0.52		Gain of catalytic residue at R880 (P = 0.0218)
MVP		0.27
ClinPred		0.95	D
GERP RS		5.7
Varity_R		0.44
gMVP		0.88

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

hg19: chr10-51040857;