13-24435159-G-T

Variant names:

• chr13-24435159-G-T
• rs1050112
• NM_006437.4:c.3982C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 15/21 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 40 publications found

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]

TPTE2P6 (HGNC:42644): (TPTE2 pseudogene 6)

ACMG classification

Our verdict: Benign. The variant received -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.

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.3982C>A	p.Pro1328Thr	missense	Exon 31 of 34	NP_006428.2	Q9UKK3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP4	ENST00000381989.4	TSL:1 MANE Select	c.3982C>A	p.Pro1328Thr	missense	Exon 31 of 34	ENSP00000371419.3	Q9UKK3
	PARP4	ENST00000908086.1		c.3982C>A	p.Pro1328Thr	missense	Exon 32 of 35	ENSP00000578145.1
	PARP4	ENST00000934618.1		c.3982C>A	p.Pro1328Thr	missense	Exon 32 of 35	ENSP00000604677.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60197 AN: 151822 Hom.: 12173 Cov.: 31

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

GnomAD2 exomes AF: 0.366 AC: 92144 AN: 251428 AF XY: 0.363

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 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.: 51 AF XY: 0.364 AC XY: 264711 AN XY: 727204

African (AFR) AF: 0.462 AC: 15471 AN: 33474

American (AMR) AF: 0.324 AC: 14477 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 9617 AN: 26136

East Asian (EAS) AF: 0.322 AC: 12791 AN: 39700

South Asian (SAS) AF: 0.306 AC: 26418 AN: 86258

European-Finnish (FIN) AF: 0.421 AC: 22485 AN: 53416

Middle Eastern (MID) AF: 0.368 AC: 2123 AN: 5762

European-Non Finnish (NFE) AF: 0.369 AC: 409873 AN: 1111936

Other (OTH) AF: 0.366 AC: 22091 AN: 60390

GnomAD4 genome AF: 0.397 AC: 60273 AN: 151940 Hom.: 12199 Cov.: 31 AF XY: 0.395 AC XY: 29355 AN XY: 74288

African (AFR) AF: 0.461 AC: 19109 AN: 41420

American (AMR) AF: 0.362 AC: 5526 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1310 AN: 3464

East Asian (EAS) AF: 0.356 AC: 1834 AN: 5152

South Asian (SAS) AF: 0.299 AC: 1437 AN: 4814

European-Finnish (FIN) AF: 0.433 AC: 4568 AN: 10556

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25316 AN: 67964

Other (OTH) AF: 0.395 AC: 830 AN: 2102

Alfa AF: 0.377 Hom.: 33257

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.061
DANN	Benign	0.61
DEOGEN2	Benign	0.049	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.00097	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.55	N
PhyloP100		-1.9
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.035
Sift	Benign	0.88	T
Sift4G	Benign	0.45	T
Polyphen		0.0070	B
Vest4		0.028
MPC		0.14
ClinPred		0.0011	T
GERP RS		-4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.018
gMVP		0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1050112; hg19: chr13-25009297; COSMIC: COSV67960416;