chr3-122535922-G-A

Variant names:

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

Variant summary

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

The ENST00000462315.5(PARP9):​c.*193C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,385,604 control chromosomes in the GnomAD database, including 17,167 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 0.14 (1557 hom., cov: 31)
  • Exomes 𝑓: 0.15 (15610 hom.)
• Consequence: PARP9 ENST00000462315.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000462315.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP9	NM_001146105.2	MANE Select	c.2080+246C>T		intron	N/A	NP_001139577.1
	PARP9	NR_170863.1		n.2593C>T		non_coding_transcript_exon	Exon 10 of 10
	PARP9	NM_001387880.1		c.*193C>T		3_prime_UTR	Exon 10 of 10	NP_001374809.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP9	ENST00000462315.5	TSL:1	c.*193C>T		3_prime_UTR	Exon 10 of 10	ENSP00000418894.1
	PARP9	ENST00000682323.1	MANE Select	c.2080+246C>T		intron	N/A	ENSP00000507390.1
	PARP9	ENST00000360356.6	TSL:1	c.2185+246C>T		intron	N/A	ENSP00000353512.2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 20969 AN: 150060 Hom.: 1556 Cov.: 31

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.0899

Gnomad ASJ AF: 0.0841

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0921

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.154 AC: 190586 AN: 1235500 Hom.: 15610 Cov.: 33 AF XY: 0.152 AC XY: 90657 AN XY: 595678

African (AFR) AF: 0.136 AC: 3670 AN: 27016

American (AMR) AF: 0.0813 AC: 1345 AN: 16552

Ashkenazi Jewish (ASJ) AF: 0.0846 AC: 1478 AN: 17476

East Asian (EAS) AF: 0.342 AC: 10833 AN: 31662

South Asian (SAS) AF: 0.0982 AC: 5430 AN: 55302

European-Finnish (FIN) AF: 0.135 AC: 4192 AN: 31144

Middle Eastern (MID) AF: 0.0672 AC: 226 AN: 3362

European-Non Finnish (NFE) AF: 0.156 AC: 156368 AN: 1002406

Other (OTH) AF: 0.139 AC: 7044 AN: 50580

GnomAD4 genome AF: 0.140 AC: 20977 AN: 150104 Hom.: 1557 Cov.: 31 AF XY: 0.139 AC XY: 10203 AN XY: 73168

African (AFR) AF: 0.132 AC: 5408 AN: 41044

American (AMR) AF: 0.0898 AC: 1351 AN: 15044

Ashkenazi Jewish (ASJ) AF: 0.0841 AC: 291 AN: 3462

East Asian (EAS) AF: 0.326 AC: 1667 AN: 5110

South Asian (SAS) AF: 0.106 AC: 506 AN: 4758

European-Finnish (FIN) AF: 0.151 AC: 1466 AN: 9734

Middle Eastern (MID) AF: 0.0929 AC: 26 AN: 280

European-Non Finnish (NFE) AF: 0.145 AC: 9806 AN: 67678

Other (OTH) AF: 0.139 AC: 290 AN: 2088

Alfa AF: 0.131 Hom.: 175

Bravo AF: 0.138

Asia WGS AF: 0.217 AC: 753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.62
PhyloP100		-0.18
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: rs3817040; hg19: chr3-122254769;