Variant 10-49879800-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003631.5(PARG):c.1861C>T(p.His621Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,166,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

PARG
NM_003631.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60

Variant links:

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]

PARG links:

PARG (HGNC:):

PARG links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1999265).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARG	NM_003631.5 linkuse as main transcript	c.1861C>T	p.His621Tyr	missense_variant	9/18	ENST00000616448.2	NP_003622.2	Q86W56-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARG	ENST00000616448.2 linkuse as main transcript	c.1861C>T	p.His621Tyr	missense_variant	9/18	1	NM_003631.5	ENSP00000484285.1		Q86W56-1

Frequencies

GnomAD3 genomes

AF:

0.000350

AC:

AN:

151638

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000659

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000707

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000243

AC:

AN:

160538

Hom.:

AF XY:

0.000213

AC XY:

AN XY:

84400

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000820

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000591

Gnomad NFE exome

AF:

0.000550

Gnomad OTH exome

AF:

0.000224

GnomAD4 exome

AF:

0.000292

AC:

296

AN:

1015318

Hom.:

Cov.:

AF XY:

0.000289

AC XY:

150

AN XY:

518652

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.0000554

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000600

Gnomad4 NFE exome

AF:

0.000364

Gnomad4 OTH exome

AF:

0.000487

GnomAD4 genome

AF:

0.000350

AC:

AN:

151638

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

AN XY:

74034

show subpopulations

Gnomad4 AFR

AF:

0.0000485

Gnomad4 AMR

AF:

0.0000659

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000190

Gnomad4 NFE

AF:

0.000707

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000389

ExAC

AF:

0.000395

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2023

The c.1861C>T (p.H621Y) alteration is located in exon 9 (coding exon 9) of the PARG gene. This alteration results from a C to T substitution at nucleotide position 1861, causing the histidine (H) at amino acid position 621 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

T;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

.;D

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.28

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Pathogenic

0.82

REVEL

Benign

0.29

Sift4G

Uncertain

0.053

T;T

Polyphen

0.77

P;P

Vest4

0.46

MVP

0.56

ClinPred

0.22

GERP RS

4.2

Varity_R

0.30

gMVP

0.55

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over