Variant chr3-122610587-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001113523.3(PARP15):c.400C>G(p.Gln134Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,399,468 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

PARP15
NM_001113523.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.22

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP15	NM_001113523.3 linkuse as main transcript	c.400C>G	p.Gln134Glu	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.400C>G	p.Gln134Glu	missense_variant	3/12	1	NM_001113523.3	ENSP00000417214.2	Q460N3-1
PARP15	ENST00000483793.5 linkuse as main transcript	c.400C>G	p.Gln134Glu	missense_variant	3/9	1		ENSP00000417785.1	C9J7L3
PARP15	ENST00000465304.5 linkuse as main transcript	n.376C>G		non_coding_transcript_exon_variant	4/14	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000637

AC:

AN:

156924

Hom.:

AF XY:

0.00

AC XY:

AN XY:

83070

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:

0.0000164

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1399468

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690228

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:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

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

Jul 20, 2021

The c.400C>G (p.Q134E) alteration is located in exon 3 (coding exon 3) of the PARP15 gene. This alteration results from a C to G substitution at nucleotide position 400, causing the glutamine (Q) at amino acid position 134 to be replaced by a glutamic acid (E). 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

0.26

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.89

D;T

M_CAP

Benign

0.0069

MetaRNN

Uncertain

0.50

D;D

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.6

D;N

REVEL

Benign

0.22

Sift

Pathogenic

0.0

D;T

Sift4G

Uncertain

0.019

D;D

Polyphen

1.0

.;D

Vest4

0.50

MVP

0.36

MPC

0.30

ClinPred

0.95

GERP RS

4.4

Varity_R

0.47

gMVP

0.59

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