rs6810306

Positions:

• chr3-122529863-G-A
• chr3-122529863-G-C
• chr3-122529863-G-T

Variant summary

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

The NM_001146105.2(PARP9):​c.2081-1120C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 151,776 control chromosomes in the GnomAD database, including 28,292 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 0.61 (28292 hom., cov: 30)
• Consequence: PARP9 NM_001146105.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490

Genes affected

PARP9 (HGNC:24118): (poly(ADP-ribose) polymerase family member 9) Enables several functions, including ADP-D-ribose binding activity; NAD+ ADP-ribosyltransferase activity; and STAT family protein binding activity. Involved in several processes, including positive regulation of nitrogen compound metabolic process; regulation of defense response; and regulation of gene expression. Located in several cellular components, including mitochondrion; nucleoplasm; and site of DNA damage. Part of protein-containing complex. Colocalizes with nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LOC105374071 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP9	NM_001146105.2	c.2081-1120C>T		intron_variant		ENST00000682323.1	NP_001139577.1
LOC105374071	XR_001740869.2	n.271-1261G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP9	ENST00000682323.1	c.2081-1120C>T		intron_variant			NM_001146105.2	ENSP00000507390	P2

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92100 AN: 151658 Hom.: 28275 Cov.: 30

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.607 AC: 92159 AN: 151776 Hom.: 28292 Cov.: 30 AF XY: 0.607 AC XY: 45013 AN XY: 74136

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.640

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.608

Alfa AF: 0.588 Hom.: 15103

Bravo AF: 0.603

Asia WGS AF: 0.678 AC: 2358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.83

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

Other links and lift over

dbSNP: rs6810306; hg19: chr3-122248710;