15-72253535-T-C

Position:

• chr15-72253535-T-C

Variant summary

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

The NM_001323532.2(PARP6):​c.1192-31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,586,508 control chromosomes in the GnomAD database, including 792,845 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 1.0 (75956 hom., cov: 31)
  • Exomes 𝑓: 1.0 (716889 hom.)
• Consequence: PARP6 NM_001323532.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

Genes affected

PARP6 (HGNC:26921): (poly(ADP-ribose) polymerase family member 6) Enables protein ADP-ribosylase activity. Involved in protein auto-ADP-ribosylation and protein mono-ADP-ribosylation. [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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP6	NM_001323532.2	c.1192-31A>G		intron_variant		ENST00000569795.6	NP_001310461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP6	ENST00000569795.6	c.1192-31A>G		intron_variant		5	NM_001323532.2	ENSP00000456348	P1

Frequencies

GnomAD3 genomes AF: 0.999 AC: 151982 AN: 152170 Hom.: 75898 Cov.: 31

Gnomad AFR AF: 0.996

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.999

GnomAD3 exomes AF: 1.00 AC: 246141 AN: 246222 Hom.: 123031 AF XY: 1.00 AC XY: 133484 AN XY: 133516

Gnomad AFR exome AF: 0.996

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome AF: 1.00 AC: 1433998 AN: 1434220 Hom.: 716889 Cov.: 24 AF XY: 1.00 AC XY: 715161 AN XY: 715258

Gnomad4 AFR exome AF: 0.996

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.999 AC: 152099 AN: 152288 Hom.: 75956 Cov.: 31 AF XY: 0.999 AC XY: 74371 AN XY: 74460

Gnomad4 AFR AF: 0.996

Gnomad4 AMR AF: 1.00

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.999

Alfa AF: 1.00 Hom.: 13779

Bravo AF: 0.999

Asia WGS AF: 1.00 AC: 3478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.41

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: rs1426166; hg19: chr15-72545876;