rs2269996

chr7-140024558-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022750.4(PARP12):c.*2C>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 0.214 in 1,613,240 control chromosomes in the GnomAD database, including 42,837 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 0.26 (5724 hom., cov: 32)
  • Exomes 𝑓: 0.21 (37113 hom.)
• Consequence: PARP12 NM_022750.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

Genes affected

PARP12 (HGNC:21919): (poly(ADP-ribose) polymerase family member 12) Enables protein ADP-ribosylase activity. Involved in protein auto-ADP-ribosylation and protein mono-ADP-ribosylation. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP12	NM_022750.4	c.*2C>T		3_prime_UTR_variant	12/12	ENST00000263549.8
PARP12	XM_047420739.1	c.*2C>T		3_prime_UTR_variant	12/12
PARP12	NR_130117.2	n.2070C>T		non_coding_transcript_exon_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP12	ENST00000263549.8	c.*2C>T		3_prime_UTR_variant	12/12	1	NM_022750.4	P1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39020 AN: 151966 Hom.: 5710 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.269

GnomAD3 exomes AF: 0.263 AC: 65991 AN: 250768 Hom.: 10848 AF XY: 0.249 AC XY: 33804 AN XY: 135584

Gnomad AFR exome AF: 0.321

Gnomad AMR exome AF: 0.435

Gnomad ASJ exome AF: 0.187

Gnomad EAS exome AF: 0.584

Gnomad SAS exome AF: 0.153

Gnomad FIN exome AF: 0.171

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.234

GnomAD4 exome AF: 0.210 AC: 306889 AN: 1461156 Hom.: 37113 Cov.: 33 AF XY: 0.207 AC XY: 150682 AN XY: 726902

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.425

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.573

Gnomad4 SAS exome AF: 0.153

Gnomad4 FIN exome AF: 0.174

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.220

GnomAD4 genome AF: 0.257 AC: 39056 AN: 152084 Hom.: 5724 Cov.: 32 AF XY: 0.257 AC XY: 19086 AN XY: 74352

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.269

Alfa AF: 0.222 Hom.: 5109

Bravo AF: 0.282

Asia WGS AF: 0.339 AC: 1180 AN: 3478

EpiCase AF: 0.205

EpiControl AF: 0.203

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.17
Dann	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs2269996; hg19: chr7-139724358; COSMIC: COSV54933200; COSMIC: COSV54933200;