NM_003631.5:c.2647+3879A>T

Variant names:

• chr10-49828924-T-A
• rs10508917
• NM_003631.5:c.2647+3879A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003631.5(PARG):​c.2647+3879A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,038 control chromosomes in the GnomAD database, including 3,295 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3295 hom., cov: 32)
• Consequence: PARG NM_003631.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

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.2647+3879A>T		intron	N/A	NP_003622.2	Q86W56-1
	PARG	NM_001303486.3		c.2401+3879A>T		intron	N/A	NP_001290415.1	Q86W56-2
	PARG	NM_001324381.3		c.2401+3879A>T		intron	N/A	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.2647+3879A>T		intron	N/A	ENSP00000484285.1	Q86W56-1
	PARG	ENST00000402038.7	TSL:1	c.2647+3879A>T		intron	N/A	ENSP00000384408.3	Q86W56-1
	PARG	ENST00000941174.1		c.2647+3879A>T		intron	N/A	ENSP00000611233.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28942 AN: 151920 Hom.: 3295 Cov.: 32

Gnomad AFR AF: 0.0759

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.0446

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.208

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.190 AC: 28943 AN: 152038 Hom.: 3295 Cov.: 32 AF XY: 0.188 AC XY: 13939 AN XY: 74292

African (AFR) AF: 0.0757 AC: 3141 AN: 41488

American (AMR) AF: 0.167 AC: 2552 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 904 AN: 3468

East Asian (EAS) AF: 0.0442 AC: 228 AN: 5162

South Asian (SAS) AF: 0.156 AC: 753 AN: 4812

European-Finnish (FIN) AF: 0.228 AC: 2408 AN: 10556

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18258 AN: 67960

Other (OTH) AF: 0.205 AC: 432 AN: 2112

Alfa AF: 0.109 Hom.: 210

Bravo AF: 0.177

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.7
DANN	Benign	0.83
PhyloP100		1.2

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: rs10508917; hg19: chr10-51036970;