3-122610313-A-G

Variant names:

• chr3-122610313-A-G
• rs2173763
• NM_001113523.3:c.307-181A>G

Variant summary

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

The NM_001113523.3(PARP15):​c.307-181A>G 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 152,158 control chromosomes in the GnomAD database, including 7,317 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 (7317 hom., cov: 32)
• Consequence: PARP15 NM_001113523.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.642
• Publications: 13 publications found

Genes affected

PARP15 (HGNC:26876): (poly(ADP-ribose) polymerase family member 15) Enables NAD+ binding activity; pentosyltransferase activity; and transcription corepressor activity. Involved in negative regulation of transcription by RNA polymerase II; protein mono-ADP-ribosylation; and protein poly-ADP-ribosylation. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP15	NM_001113523.3	c.307-181A>G		intron_variant	Intron 2 of 11	ENST00000464300.7	NP_001106995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP15	ENST00000464300.7	c.307-181A>G		intron_variant	Intron 2 of 11	1	NM_001113523.3	ENSP00000417214.2
PARP15	ENST00000483793.5	c.307-181A>G		intron_variant	Intron 2 of 8	1		ENSP00000417785.1
PARP15	ENST00000465304.5	n.283-181A>G		intron_variant	Intron 3 of 13	2

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32905 AN: 152038 Hom.: 7289 Cov.: 32

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0556

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0598

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.0685

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.217 AC: 32992 AN: 152158 Hom.: 7317 Cov.: 32 AF XY: 0.213 AC XY: 15848 AN XY: 74396

African (AFR) AF: 0.571 AC: 23674 AN: 41460

American (AMR) AF: 0.128 AC: 1953 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0556 AC: 193 AN: 3472

East Asian (EAS) AF: 0.164 AC: 851 AN: 5176

South Asian (SAS) AF: 0.119 AC: 574 AN: 4820

European-Finnish (FIN) AF: 0.0598 AC: 635 AN: 10610

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0685 AC: 4659 AN: 68008

Other (OTH) AF: 0.184 AC: 388 AN: 2110

Alfa AF: 0.143 Hom.: 6699

Bravo AF: 0.239

Asia WGS AF: 0.182 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.38
DANN	Benign	0.63
PhyloP100		-0.64
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: rs2173763; hg19: chr3-122329160;