Variant chr5-50761867-A-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_024615.4(PARP8):c.392A>G(p.Asn131Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000482 in 1,452,358 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: 0.0000048 ( 0 hom. )

Consequence

PARP8
NM_024615.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.48

Variant links:

Genes affected

PARP8 (HGNC:26124): (poly(ADP-ribose) polymerase family member 8) Enables protein ADP-ribosylase activity. Involved in protein auto-ADP-ribosylation and protein mono-ADP-ribosylation. [provided by Alliance of Genome Resources, Apr 2022]

PARP8 links:

PARP8 (HGNC:):

PARP8 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
PARP8	NM_024615.4 linkuse as main transcript	c.392A>G	p.Asn131Ser	missense_variant	6/26	ENST00000281631.10	NP_078891.2	Q8N3A8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP8	ENST00000281631.10 linkuse as main transcript	c.392A>G	p.Asn131Ser	missense_variant	6/26	1	NM_024615.4	ENSP00000281631.4		Q8N3A8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

247022

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133714

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:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000482

AC:

AN:

1452358

Hom.:

Cov.:

AF XY:

0.00000830

AC XY:

AN XY:

722644

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:

0.00000543

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Sep 26, 2023

The c.392A>G (p.N131S) alteration is located in exon 7 (coding exon 6) of the PARP8 gene. This alteration results from a A to G substitution at nucleotide position 392, causing the asparagine (N) at amino acid position 131 to be replaced by a serine (S). 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

0.19

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.050

T;T;.;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

.;D;D;D

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.56

D;D;D;D

MetaSVM

Benign

-0.71

MutationAssessor

Benign

0.84

L;L;L;.

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.7

N;N;N;N

REVEL

Benign

0.13

Sift

Uncertain

0.0090

D;D;D;D

Sift4G

Benign

0.26

T;T;T;T

Polyphen

0.96

P;P;D;.

Vest4

0.68

MutPred

0.16

Gain of phosphorylation at N131 (P = 0.0052);Gain of phosphorylation at N131 (P = 0.0052);Gain of phosphorylation at N131 (P = 0.0052);.;

MVP

0.59

MPC

0.63

ClinPred

0.79

GERP RS

5.5

Varity_R

0.19

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

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