Variant chr3-122610623-G-C 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.436G>C(p.Glu146Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000343 in 1,399,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.000034 ( 0 hom. )

Consequence

PARP15
NM_001113523.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.276

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=0.10437867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP15	NM_001113523.3 linkuse as main transcript	c.436G>C	p.Glu146Gln	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.436G>C	p.Glu146Gln	missense_variant	3/12	1	NM_001113523.3	ENSP00000417214.2	Q460N3-1
PARP15	ENST00000483793.5 linkuse as main transcript	c.436G>C	p.Glu146Gln	missense_variant	3/9	1		ENSP00000417785.1	C9J7L3
PARP15	ENST00000465304.5 linkuse as main transcript	n.412G>C		non_coding_transcript_exon_variant	4/14	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000255

AC:

AN:

156850

Hom.:

AF XY:

0.0000120

AC XY:

AN XY:

83024

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:

0.00

Gnomad NFE exome

AF:

0.0000658

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000343

AC:

AN:

1399252

Hom.:

Cov.:

AF XY:

0.0000464

AC XY:

AN XY:

690150

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:

0.0000399

Gnomad4 OTH exome

AF:

0.0000517

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000393

AC:

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

Nov 26, 2024

The c.436G>C (p.E146Q) alteration is located in exon 3 (coding exon 3) of the PARP15 gene. This alteration results from a G to C substitution at nucleotide position 436, causing the glutamic acid (E) at amino acid position 146 to be replaced by a glutamine (Q). 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

0.16

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.8

DANN

Benign

0.39

DEOGEN2

Benign

0.0027

T;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.36

N;N

REVEL

Benign

0.036

Sift

Benign

0.50

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.99

.;D

Vest4

0.15

MVP

0.21

MPC

0.18

ClinPred

0.051

GERP RS

3.0

Varity_R

0.036

gMVP

0.20

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

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