10-49842019-G-T

Variant names:

• chr10-49842019-G-T
• NM_003631.5:c.2472C>A
• PARG p.Ile824Ile

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003631.5(PARG):​c.2472C>A​(p.Ile824Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: PARG NM_003631.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-2.18 with no splicing effect.

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.2472C>A	p.Ile824Ile	synonymous	Exon 15 of 18	NP_003622.2	Q86W56-1
	PARG	NM_001303486.3		c.2226C>A	p.Ile742Ile	synonymous	Exon 15 of 18	NP_001290415.1	Q86W56-2
	PARG	NM_001324381.3		c.2226C>A	p.Ile742Ile	synonymous	Exon 15 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.2472C>A	p.Ile824Ile	synonymous	Exon 15 of 18	ENSP00000484285.1	Q86W56-1
	PARG	ENST00000402038.7	TSL:1	c.2472C>A	p.Ile824Ile	synonymous	Exon 16 of 19	ENSP00000384408.3	Q86W56-1
	PARG	ENST00000941174.1		c.2472C>A	p.Ile824Ile	synonymous	Exon 15 of 18	ENSP00000611233.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.87
DANN	Benign	0.85
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-51050065;