Genetic Variant PARP15:c.*1504G>A (chr3-122637604-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001113523.3(PARP15):c.*1504G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0541 in 152,010 control chromosomes in the GnomAD database, including 284 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 0.054 ( 284 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

PARP15
NM_001113523.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.234

Publications

0 publications found

Variant links:

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]

PARP15 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0633 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113523.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PARP15	NM_001113523.3	MANE Select	c.*1504G>A	3_prime_UTR	Exon 12 of 12	NP_001106995.1
PARP15	NM_001308320.2		c.*1504G>A	3_prime_UTR	Exon 9 of 9	NP_001295249.1
PARP15	NM_152615.3		c.*1504G>A	3_prime_UTR	Exon 8 of 8	NP_689828.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP15	ENST00000464300.7	TSL:1 MANE Select	c.*1504G>A		3_prime_UTR	Exon 12 of 12	ENSP00000417214.2
	PARP15	ENST00000483793.5	TSL:1	c.*1504G>A		3_prime_UTR	Exon 9 of 9	ENSP00000417785.1

Frequencies

GnomAD3 genomes

AF:

0.0541

AC:

8216

AN:

151892

Hom.:

281

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0127

Gnomad AMI

AF:

0.0824

Gnomad AMR

AF:

0.0662

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.0235

Gnomad SAS

AF:

0.0498

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0646

Gnomad OTH

AF:

0.0660

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0541

AC:

8220

AN:

152010

Hom.:

284

Cov.:

AF XY:

0.0569

AC XY:

4230

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.0127

AC:

528

AN:

41456

American (AMR)

AF:

0.0667

AC:

1018

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

364

AN:

3468

East Asian (EAS)

AF:

0.0236

AC:

122

AN:

5170

South Asian (SAS)

AF:

0.0494

AC:

238

AN:

4814

European-Finnish (FIN)

AF:

0.125

AC:

1319

AN:

10532

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0646

AC:

4389

AN:

67990

Other (OTH)

AF:

0.0649

AC:

137

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

390

781

1171

1562

1952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0582

Hom.:

556

Bravo

AF:

0.0488

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

2.0

(source)

DANN

Benign

0.16

PhyloP100

-0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over