Variant rs1050112 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006437.4(PARP4):c.3982C>A(p.Pro1328Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,613,732 control chromosomes in the GnomAD database, including 111,041 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 12199 hom., cov: 31)

Exomes 𝑓: 0.37 ( 98842 hom. )

Consequence

PARP4
NM_006437.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.87

Variant links:

Genes affected

PARP4 (HGNC:271): (poly(ADP-ribose) polymerase family member 4) This gene encodes poly(ADP-ribosyl)transferase-like 1 protein, which is capable of catalyzing a poly(ADP-ribosyl)ation reaction. This protein has a catalytic domain which is homologous to that of poly (ADP-ribosyl) transferase, but lacks an N-terminal DNA binding domain which activates the C-terminal catalytic domain of poly (ADP-ribosyl) transferase. Since this protein is not capable of binding DNA directly, its transferase activity may be activated by other factors such as protein-protein interaction mediated by the extensive carboxyl terminus. [provided by RefSeq, Jul 2008]

PARP4 links:

TPTE2P6 (HGNC:):

TPTE2P6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.72718E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP4	NM_006437.4 linkuse as main transcript	c.3982C>A	p.Pro1328Thr	missense_variant	31/34	ENST00000381989.4	NP_006428.2	Q9UKK3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP4	ENST00000381989.4 linkuse as main transcript	c.3982C>A	p.Pro1328Thr	missense_variant	31/34	1	NM_006437.4	ENSP00000371419.3		Q9UKK3
TPTE2P6	ENST00000445572.5 linkuse as main transcript	n.233+25855G>T		intron_variant		6

Frequencies

GnomAD3 genomes

AF:

0.396

AC:

60197

AN:

151822

Hom.:

12173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.461

Gnomad AMI

AF:

0.240

Gnomad AMR

AF:

0.362

Gnomad ASJ

AF:

0.378

Gnomad EAS

AF:

0.357

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.372

Gnomad OTH

AF:

0.390

GnomAD3 exomes

AF:

0.366

AC:

92144

AN:

251428

Hom.:

17189

AF XY:

0.363

AC XY:

49281

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.463

Gnomad AMR exome

AF:

0.316

Gnomad ASJ exome

AF:

0.372

Gnomad EAS exome

AF:

0.353

Gnomad SAS exome

AF:

0.304

Gnomad FIN exome

AF:

0.423

Gnomad NFE exome

AF:

0.375

Gnomad OTH exome

AF:

0.373

GnomAD4 exome

AF:

0.366

AC:

535346

AN:

1461792

Hom.:

98842

Cov.:

AF XY:

0.364

AC XY:

264711

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.462

Gnomad4 AMR exome

AF:

0.324

Gnomad4 ASJ exome

AF:

0.368

Gnomad4 EAS exome

AF:

0.322

Gnomad4 SAS exome

AF:

0.306

Gnomad4 FIN exome

AF:

0.421

Gnomad4 NFE exome

AF:

0.369

Gnomad4 OTH exome

AF:

0.366

GnomAD4 genome

AF:

0.397

AC:

60273

AN:

151940

Hom.:

12199

Cov.:

AF XY:

0.395

AC XY:

29355

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.461

Gnomad4 AMR

AF:

0.362

Gnomad4 ASJ

AF:

0.378

Gnomad4 EAS

AF:

0.356

Gnomad4 SAS

AF:

0.299

Gnomad4 FIN

AF:

0.433

Gnomad4 NFE

AF:

0.372

Gnomad4 OTH

AF:

0.395

Alfa

AF:

0.373

Hom.:

23227

Bravo

AF:

0.391

TwinsUK

AF:

0.371

AC:

1377

ALSPAC

AF:

0.357

AC:

1377

ESP6500AA

AF:

0.471

AC:

2075

ESP6500EA

AF:

0.373

AC:

3204

ExAC

AF:

0.369

AC:

44761

Asia WGS

AF:

0.382

AC:

1327

AN:

3478

EpiCase

AF:

0.372

EpiControl

AF:

0.369

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.061

DANN

Benign

0.61

DEOGEN2

Benign

0.049

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.41

MetaRNN

Benign

0.00097

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.51

REVEL

Benign

0.035

Sift

Benign

0.88

Sift4G

Benign

0.45

Polyphen

0.0070

Vest4

0.028

MPC

0.14

ClinPred

0.0011

GERP RS

-4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.018

gMVP

0.23

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over