3-122556625-T-G

Variant names:

• chr3-122556625-T-G
• rs1500530
• NM_001146105.2:c.50-504A>C

Variant summary

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

The NM_001146105.2(PARP9):​c.50-504A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,942 control chromosomes in the GnomAD database, including 4,151 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 0.22 (4151 hom., cov: 31)
• Consequence: PARP9 NM_001146105.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP9	NM_001146105.2	c.50-504A>C		intron_variant	Intron 3 of 10	ENST00000682323.1	NP_001139577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP9	ENST00000682323.1	c.50-504A>C		intron_variant	Intron 3 of 10		NM_001146105.2	ENSP00000507390.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33036 AN: 151820 Hom.: 4150 Cov.: 31

Gnomad AFR AF: 0.0939

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.217 AC: 33044 AN: 151942 Hom.: 4151 Cov.: 31 AF XY: 0.223 AC XY: 16562 AN XY: 74260

African (AFR) AF: 0.0938 AC: 3889 AN: 41474

American (AMR) AF: 0.189 AC: 2879 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3464

East Asian (EAS) AF: 0.235 AC: 1219 AN: 5178

South Asian (SAS) AF: 0.241 AC: 1161 AN: 4822

European-Finnish (FIN) AF: 0.362 AC: 3803 AN: 10516

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18546 AN: 67916

Other (OTH) AF: 0.217 AC: 458 AN: 2114

Alfa AF: 0.143 Hom.: 408

Bravo AF: 0.199

Asia WGS AF: 0.222 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Benign	0.81
PhyloP100		2.4
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: rs1500530; hg19: chr3-122275472;