rs3735351

Positions:

• chr7-140024942-G-C

Variant summary

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

The ENST00000263549.8(PARP12):​c.1781-57C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0934 in 1,523,382 control chromosomes in the GnomAD database, including 7,333 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 0.076 (536 hom., cov: 32)
  • Exomes 𝑓: 0.095 (6797 hom.)
• Consequence: PARP12 ENST00000263549.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP12	NM_022750.4	c.1781-57C>G		intron_variant		ENST00000263549.8	NP_073587.1
PARP12	XM_047420739.1	c.1886-57C>G		intron_variant			XP_047276695.1
PARP12	NR_130117.2	n.1743-57C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP12	ENST00000263549.8	c.1781-57C>G		intron_variant		1	NM_022750.4	ENSP00000263549	P1

Frequencies

GnomAD3 genomes AF: 0.0759 AC: 11537 AN: 152080 Hom.: 536 Cov.: 32

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0707

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0508

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.0450

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0921

GnomAD4 exome AF: 0.0954 AC: 130777 AN: 1371184 Hom.: 6797 AF XY: 0.0940 AC XY: 64089 AN XY: 681536

Gnomad4 AFR exome AF: 0.0306

Gnomad4 AMR exome AF: 0.0552

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.0521

Gnomad4 SAS exome AF: 0.0299

Gnomad4 FIN exome AF: 0.0535

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.0877

GnomAD4 genome AF: 0.0758 AC: 11537 AN: 152198 Hom.: 536 Cov.: 32 AF XY: 0.0725 AC XY: 5398 AN XY: 74422

Gnomad4 AFR AF: 0.0330

Gnomad4 AMR AF: 0.0706

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.0514

Gnomad4 SAS AF: 0.0257

Gnomad4 FIN AF: 0.0450

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0916

Alfa AF: 0.0417 Hom.: 40

Bravo AF: 0.0782

Asia WGS AF: 0.0370 AC: 128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.73

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: rs3735351; hg19: chr7-139724742;