3-122535922-G-C

Variant names:

• chr3-122535922-G-C
• rs3817040
• ENST00000462315.5:c.*193C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000462315.5(PARP9):​c.*193C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000809 in 1,235,938 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: PARP9 ENST00000462315.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP9	NM_001146105.2	c.2080+246C>G		intron_variant	Intron 10 of 10	ENST00000682323.1	NP_001139577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP9	ENST00000682323.1	c.2080+246C>G		intron_variant	Intron 10 of 10		NM_001146105.2	ENSP00000507390.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.09e-7 AC: 1 AN: 1235938 Hom.: 0 Cov.: 33 AF XY: 0.00000168 AC XY: 1 AN XY: 595890

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27030

American (AMR) AF: 0.00 AC: 0 AN: 16560

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17482

East Asian (EAS) AF: 0.00 AC: 0 AN: 31724

South Asian (SAS) AF: 0.00 AC: 0 AN: 55320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3364

European-Non Finnish (NFE) AF: 9.97e-7 AC: 1 AN: 1002672

Other (OTH) AF: 0.00 AC: 0 AN: 50610

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.66
DANN	Benign	0.43
PhyloP100		-0.18

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: rs3817040; hg19: chr3-122254769;