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3-122610643-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001113523.3(PARP15):c.456C>A(p.Phe152Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000438 in 1,551,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

PARP15
NM_001113523.3 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0730
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.040077627).
BP6
Variant 3-122610643-C-A is Benign according to our data. Variant chr3-122610643-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3208738.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PARP15NM_001113523.3 linkuse as main transcriptc.456C>A p.Phe152Leu missense_variant 3/12 ENST00000464300.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PARP15ENST00000464300.7 linkuse as main transcriptc.456C>A p.Phe152Leu missense_variant 3/121 NM_001113523.3 P1Q460N3-1
PARP15ENST00000483793.5 linkuse as main transcriptc.456C>A p.Phe152Leu missense_variant 3/91
PARP15ENST00000465304.5 linkuse as main transcriptn.432C>A non_coding_transcript_exon_variant 4/142

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152176
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000383
AC:
6
AN:
156528
Hom.:
0
AF XY:
0.0000483
AC XY:
4
AN XY:
82870
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000596
Gnomad NFE exome
AF:
0.0000825
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000457
AC:
64
AN:
1399232
Hom.:
0
Cov.:
30
AF XY:
0.0000464
AC XY:
32
AN XY:
690126
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000406
Gnomad4 NFE exome
AF:
0.0000547
Gnomad4 OTH exome
AF:
0.0000517
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152176
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000386
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000393
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsFeb 26, 2024This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.80
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.72
Cadd
Benign
4.4
Dann
Benign
0.55
DEOGEN2
Benign
0.0014
T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.56
T;T
M_CAP
Benign
0.0014
T
MetaRNN
Benign
0.040
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.0050
N;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
2.0
N;N
REVEL
Benign
0.070
Sift
Benign
1.0
T;T
Sift4G
Benign
0.87
T;T
Polyphen
0.0040
.;B
Vest4
0.082
MVP
0.16
MPC
0.046
ClinPred
0.026
T
GERP RS
1.2
Varity_R
0.048
gMVP
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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.

Other links and lift over

dbSNP: rs747514786; hg19: chr3-122329490; API