rs6810306

Variant names:

• chr3-122529863-G-A
• rs6810306
• NM_001146105.2:c.2081-1120C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146105.2. 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
	PARP9	NM_001146105.2	MANE Select	c.2081-1120C>T		intron	N/A	NP_001139577.1	Q8IXQ6-2
	PARP9	NM_001146102.2		c.2186-1120C>T		intron	N/A	NP_001139574.1	Q8IXQ6-1
	PARP9	NM_001387871.1		c.2186-1120C>T		intron	N/A	NP_001374800.1	Q8IXQ6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP9	ENST00000682323.1	MANE Select	c.2081-1120C>T		intron	N/A	ENSP00000507390.1	Q8IXQ6-2
	PARP9	ENST00000360356.6	TSL:1	c.2186-1120C>T		intron	N/A	ENSP00000353512.2	Q8IXQ6-1
	PARP9	ENST00000477522.6	TSL:1	c.2081-1120C>T		intron	N/A	ENSP00000419506.1	Q8IXQ6-2

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

African (AFR) AF: 0.665 AC: 27542 AN: 41392

American (AMR) AF: 0.490 AC: 7467 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2216 AN: 3464

East Asian (EAS) AF: 0.771 AC: 3979 AN: 5160

South Asian (SAS) AF: 0.631 AC: 3037 AN: 4812

European-Finnish (FIN) AF: 0.594 AC: 6213 AN: 10468

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.584 AC: 39692 AN: 67912

Other (OTH) AF: 0.608 AC: 1283 AN: 2110

Alfa AF: 0.589 Hom.: 16634

Bravo AF: 0.603

Asia WGS AF: 0.678 AC: 2358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		0.49
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: rs6810306; hg19: chr3-122248710;