Variant 3-122610512-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001113523.3(PARP15):c.325A>G(p.Ser109Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000643 in 1,399,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

PARP15
NM_001113523.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0710

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:

PARP15 (HGNC:):

PARP15 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15577552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP15	NM_001113523.3 linkuse as main transcript	c.325A>G	p.Ser109Gly	missense_variant	3/12	ENST00000464300.7	NP_001106995.1	Q460N3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PARP15	ENST00000464300.7 linkuse as main transcript	c.325A>G	p.Ser109Gly	missense_variant	3/12	1	NM_001113523.3	ENSP00000417214.2	Q460N3-1
PARP15	ENST00000483793.5 linkuse as main transcript	c.325A>G	p.Ser109Gly	missense_variant	3/9	1		ENSP00000417785.1	C9J7L3
PARP15	ENST00000465304.5 linkuse as main transcript	n.301A>G		non_coding_transcript_exon_variant	4/14	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000128

AC:

AN:

156220

Hom.:

AF XY:

0.0000242

AC XY:

AN XY:

82802

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000813

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000643

AC:

AN:

1399212

Hom.:

Cov.:

AF XY:

0.00000580

AC XY:

AN XY:

690106

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000281

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000741

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2024

The c.325A>G (p.S109G) alteration is located in exon 3 (coding exon 3) of the PARP15 gene. This alteration results from a A to G substitution at nucleotide position 325, causing the serine (S) at amino acid position 109 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.9

DANN

Benign

0.93

DEOGEN2

Benign

0.022

T;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;.

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.12

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.50

.;P

Vest4

0.32

MVP

0.14

MPC

0.11

ClinPred

0.27

GERP RS

-8.8

Varity_R

0.13

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over