13-24445117-A-G

Position:

• chr13-24445117-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006437.4(PARP4):​c.3367-1387T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,352 control chromosomes in the GnomAD database, including 19,625 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (19625 hom., cov: 31)
• Consequence: PARP4 NM_006437.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.644

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP4	NM_006437.4	c.3367-1387T>C		intron_variant		ENST00000381989.4	NP_006428.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP4	ENST00000381989.4	c.3367-1387T>C		intron_variant		1	NM_006437.4	ENSP00000371419.3
TPTE2P6	ENST00000445572.5	n.233+35813A>G		intron_variant		6

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73599 AN: 151234 Hom.: 19629 Cov.: 31

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.501

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.486 AC: 73608 AN: 151352 Hom.: 19625 Cov.: 31 AF XY: 0.491 AC XY: 36297 AN XY: 73910

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.498

Alfa AF: 0.514 Hom.: 2606

Bravo AF: 0.480

Asia WGS AF: 0.574 AC: 1997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

Other links and lift over

dbSNP: rs7984513; hg19: chr13-25019255;