Genetic Variant PARP4:p.Ser1685Phe (chr13-24421240-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006437.4(PARP4):c.5054C>T(p.Ser1685Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000401 in 1,346,192 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000038 ( 1 hom. )

Consequence

PARP4
NM_006437.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.97

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006437.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP4	NM_006437.4	MANE Select	c.5054C>T	p.Ser1685Phe	missense	Exon 34 of 34	NP_006428.2	Q9UKK3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PARP4	ENST00000381989.4	TSL:1 MANE Select	c.5054C>T	p.Ser1685Phe	missense	Exon 34 of 34	ENSP00000371419.3	Q9UKK3
PARP4	ENST00000908086.1		c.5054C>T	p.Ser1685Phe	missense	Exon 35 of 35	ENSP00000578145.1
PARP4	ENST00000934618.1		c.5054C>T	p.Ser1685Phe	missense	Exon 35 of 35	ENSP00000604677.1

Frequencies

GnomAD3 genomes

AF:

0.0000536

AC:

AN:

149220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000674

Gnomad ASJ

AF:

0.000579

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000445

Gnomad OTH

AF:

0.000996

GnomAD2 exomes

AF:

0.0000257

AC:

AN:

77742

AF XY:

0.0000260

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000890

GnomAD4 exome

AF:

0.0000384

AC:

AN:

1196972

Hom.:

Cov.:

AF XY:

0.0000459

AC XY:

AN XY:

587768

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26262

American (AMR)

AF:

0.0000427

AC:

AN:

23426

Ashkenazi Jewish (ASJ)

AF:

0.000211

AC:

AN:

18990

East Asian (EAS)

AF:

0.00

AC:

AN:

34582

South Asian (SAS)

AF:

0.0000326

AC:

AN:

61330

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45456

Middle Eastern (MID)

AF:

0.00466

AC:

AN:

3436

European-Non Finnish (NFE)

AF:

0.0000225

AC:

AN:

933192

Other (OTH)

AF:

0.0000398

AC:

AN:

50298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000536

AC:

AN:

149220

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

72596

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40412

American (AMR)

AF:

0.0000674

AC:

AN:

14834

Ashkenazi Jewish (ASJ)

AF:

0.000579

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5114

South Asian (SAS)

AF:

0.00

AC:

AN:

4566

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10126

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000445

AC:

AN:

67484

Other (OTH)

AF:

0.000996

AC:

AN:

2008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.79

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.51

MetaSVM

Uncertain

0.21

MutationAssessor

Uncertain

2.4

PhyloP100

4.0

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.58

Sift

Uncertain

0.011

Sift4G

Uncertain

0.043

Polyphen

1.0

Vest4

0.47

MVP

0.92

MPC

0.58

ClinPred

0.94

GERP RS

3.2

Varity_R

0.14

gMVP

0.44

Mutation Taster

=89/11

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over