3-122613219-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001113523.3(PARP15):c.722T>C(p.Leu241Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00112 in 1,551,840 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00057 (8 hom.)
• Consequence: PARP15 NM_001113523.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.47

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0057423413).
• BP6: Variant 3-122613219-T-C is Benign according to our data. Variant chr3-122613219-T-C is described in ClinVar as [Benign]. Clinvar id is 767926.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00615 (937/152356) while in subpopulation AFR AF= 0.0217 (901/41582). AF 95% confidence interval is 0.0205. There are 8 homozygotes in gnomad4. There are 446 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP15	NM_001113523.3	c.722T>C	p.Leu241Ser	missense_variant	4/12	ENST00000464300.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP15	ENST00000464300.7	c.722T>C	p.Leu241Ser	missense_variant	4/12	1	NM_001113523.3	P1
PARP15	ENST00000483793.5	c.543+2489T>C		intron_variant		1
PARP15	ENST00000465304.5	n.698T>C		non_coding_transcript_exon_variant	5/14	2

Frequencies

GnomAD3 genomes AF: 0.00614 AC: 934 AN: 152238 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00121 AC: 190 AN: 157004 Hom.: 4 AF XY: 0.000891 AC XY: 74 AN XY: 83020

Gnomad AFR exome AF: 0.0208

Gnomad AMR exome AF: 0.000647

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000878

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000674

GnomAD4 exome AF: 0.000574 AC: 804 AN: 1399484 Hom.: 8 Cov.: 31 AF XY: 0.000466 AC XY: 322 AN XY: 690248

Gnomad4 AFR exome AF: 0.0228

Gnomad4 AMR exome AF: 0.000784

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000252

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000927

Gnomad4 OTH exome AF: 0.000689

GnomAD4 genome AF: 0.00615 AC: 937 AN: 152356 Hom.: 8 Cov.: 32 AF XY: 0.00599 AC XY: 446 AN XY: 74496

Gnomad4 AFR AF: 0.0217

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00267 Hom.: 3

Bravo AF: 0.00721

ESP6500AA AF: 0.0289 AC: 40

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00214 AC: 54

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 19, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.29
Cadd	Benign	19
Dann	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.0086
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.0057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.5	H
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.27
MVP		0.15
MPC		0.20
ClinPred		0.18	T
GERP RS		3.1
Varity_R		0.18
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs115551100; hg19: chr3-122332066;