3-122630292-T-C

Variant names:

• chr3-122630292-T-C
• rs10511411
• NM_001113523.3:c.1439-1794T>C

Variant summary

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

The NM_001113523.3(PARP15):​c.1439-1794T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 152,262 control chromosomes in the GnomAD database, including 121 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 0.038 (121 hom., cov: 32)
• Consequence: PARP15 NM_001113523.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP15	NM_001113523.3	c.1439-1794T>C		intron_variant	Intron 9 of 11	ENST00000464300.7	NP_001106995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP15	ENST00000464300.7	c.1439-1794T>C		intron_variant	Intron 9 of 11	1	NM_001113523.3	ENSP00000417214.2

Frequencies

GnomAD3 genomes AF: 0.0380 AC: 5787 AN: 152146 Hom.: 120 Cov.: 32

Gnomad AFR AF: 0.00982

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0522

Gnomad ASJ AF: 0.0482

Gnomad EAS AF: 0.0277

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.0379

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0529

Gnomad OTH AF: 0.0551

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

GnomAD4 genome AF: 0.0381 AC: 5797 AN: 152262 Hom.: 121 Cov.: 32 AF XY: 0.0378 AC XY: 2818 AN XY: 74462

African (AFR) AF: 0.00982 AC: 408 AN: 41550

American (AMR) AF: 0.0523 AC: 799 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0482 AC: 167 AN: 3468

East Asian (EAS) AF: 0.0279 AC: 145 AN: 5190

South Asian (SAS) AF: 0.0197 AC: 95 AN: 4826

European-Finnish (FIN) AF: 0.0379 AC: 402 AN: 10610

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0529 AC: 3595 AN: 68014

Other (OTH) AF: 0.0578 AC: 122 AN: 2110

Alfa AF: 0.0472 Hom.: 31

Bravo AF: 0.0402

Asia WGS AF: 0.0300 AC: 103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.36
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism

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: rs10511411; hg19: chr3-122349139;