Variant 13-24421254-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_006437.4(PARP4):c.5040A>G(p.Glu1680=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00781 in 1,310,920 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 3 hom., cov: 26)

Exomes 𝑓: 0.0081 ( 31 hom. )

Consequence

PARP4
NM_006437.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.395

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:42644): (TPTE2 pseudogene 6)

TPTE2P6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 13-24421254-T-C is Benign according to our data. Variant chr13-24421254-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2643684.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.395 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP4	NM_006437.4 linkuse as main transcript	c.5040A>G	p.Glu1680=	synonymous_variant	34/34	ENST00000381989.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP4	ENST00000381989.4 linkuse as main transcript	c.5040A>G	p.Glu1680=	synonymous_variant	34/34	1	NM_006437.4	P1
TPTE2P6	ENST00000445572.5 linkuse as main transcript	n.233+11950T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00523

AC:

777

AN:

148600

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00358

Gnomad ASJ

AF:

0.0143

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00154

Gnomad FIN

AF:

0.00349

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00815

Gnomad OTH

AF:

0.00549

GnomAD3 exomes

AF:

0.00468

AC:

343

AN:

73230

Hom.:

AF XY:

0.00460

AC XY:

167

AN XY:

36334

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00321

Gnomad ASJ exome

AF:

0.0167

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.00321

Gnomad NFE exome

AF:

0.00803

Gnomad OTH exome

AF:

0.00427

GnomAD4 exome

AF:

0.00814

AC:

9463

AN:

1162202

Hom.:

Cov.:

AF XY:

0.00811

AC XY:

4624

AN XY:

570280

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00311

Gnomad4 ASJ exome

AF:

0.0157

Gnomad4 EAS exome

AF:

0.0000291

Gnomad4 SAS exome

AF:

0.00182

Gnomad4 FIN exome

AF:

0.00297

Gnomad4 NFE exome

AF:

0.00938

Gnomad4 OTH exome

AF:

0.00672

GnomAD4 genome

AF:

0.00522

AC:

777

AN:

148718

Hom.:

Cov.:

AF XY:

0.00481

AC XY:

348

AN XY:

72418

show subpopulations

Gnomad4 AFR

AF:

0.00181

Gnomad4 AMR

AF:

0.00358

Gnomad4 ASJ

AF:

0.0143

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00155

Gnomad4 FIN

AF:

0.00349

Gnomad4 NFE

AF:

0.00815

Gnomad4 OTH

AF:

0.00543

Alfa

AF:

0.00574

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

PARP4: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.0

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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