Variant chr10-49879716-T-C 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.1945A>G(p.Met649Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000349 in 1,575,100 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000033 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

PARG
NM_003631.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

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=0.22709084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARG	NM_003631.5 linkuse as main transcript	c.1945A>G	p.Met649Val	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.1945A>G	p.Met649Val	missense_variant	9/18	1	NM_003631.5	ENSP00000484285.1		Q86W56-1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000669

AC:

AN:

194336

Hom.:

AF XY:

0.0000677

AC XY:

AN XY:

103348

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000144

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000693

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000977

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000351

AC:

AN:

1422864

Hom.:

Cov.:

AF XY:

0.0000341

AC XY:

AN XY:

704104

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.000103

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000376

Gnomad4 OTH exome

AF:

0.0000679

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000676

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000833

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

Nov 25, 2024

The c.1945A>G (p.M649V) alteration is located in exon 9 (coding exon 9) of the PARG gene. This alteration results from a A to G substitution at nucleotide position 1945, causing the methionine (M) at amino acid position 649 to be replaced by a valine (V). 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

0.15

BayesDel_addAF

Uncertain

0.035

BayesDel_noAF

Uncertain

0.030

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.024

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.80

.;T

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.81

L;L

PrimateAI

Pathogenic

0.80

REVEL

Uncertain

0.52

Sift4G

Benign

0.34

T;T

Polyphen

0.22

B;B

Vest4

0.41

MutPred

0.57

Gain of methylation at K648 (P = 0.0197);Gain of methylation at K648 (P = 0.0197);

MVP

0.39

ClinPred

0.12

GERP RS

4.2

Varity_R

0.35

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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