Variant 3-122536993-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001146105.2(PARP9):c.1846A>G(p.Thr616Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00331 in 1,613,946 control chromosomes in the GnomAD database, including 171 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 79 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 92 hom. )

Consequence

PARP9
NM_001146105.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.76

Variant links:

Genes affected

PARP9 (HGNC:24118): (poly(ADP-ribose) polymerase family member 9) Enables several functions, including ADP-D-ribose binding activity; NAD+ ADP-ribosyltransferase activity; and STAT family protein binding activity. Involved in several processes, including positive regulation of nitrogen compound metabolic process; regulation of defense response; and regulation of gene expression. Located in several cellular components, including mitochondrion; nucleoplasm; and site of DNA damage. Part of protein-containing complex. Colocalizes with nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PARP9 links:

PARP9 (HGNC:):

PARP9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026766956).

BP6

Variant 3-122536993-T-C is Benign according to our data. Variant chr3-122536993-T-C is described in ClinVar as [Benign]. Clinvar id is 790541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP9	NM_001146105.2 linkuse as main transcript	c.1846A>G	p.Thr616Ala	missense_variant	9/11	ENST00000682323.1	NP_001139577.1	Q8IXQ6-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP9	ENST00000682323.1 linkuse as main transcript	c.1846A>G	p.Thr616Ala	missense_variant	9/11		NM_001146105.2	ENSP00000507390.1		Q8IXQ6-2

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2743

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0634

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.00450

AC:

1131

AN:

251328

Hom.:

AF XY:

0.00326

AC XY:

443

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.0650

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.00178

AC:

2601

AN:

1461664

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

1092

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.0672

Gnomad4 AMR exome

AF:

0.00233

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.00353

GnomAD4 genome

AF:

0.0180

AC:

2743

AN:

152282

Hom.:

Cov.:

AF XY:

0.0175

AC XY:

1301

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0632

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.00326

Hom.:

Bravo

AF:

0.0200

ESP6500AA

AF:

0.0638

AC:

281

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00555

AC:

674

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.17

DANN

Benign

0.59

DEOGEN2

Benign

0.0089

.;T;T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.57

.;T;T;T;T

MetaRNN

Benign

0.0027

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.2

.;.;L;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.73

N;N;N;N;N

REVEL

Benign

0.0070

Sift

Benign

0.82

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0020

B;B;B;B;.

Vest4

0.082

MVP

0.28

MPC

0.14

ClinPred

0.0046

GERP RS

-3.0

Varity_R

0.021

gMVP

0.21

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