chr5-50794271-A-T

Position:

• chr5-50794271-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024615.4(PARP8):​c.802A>T​(p.Asn268Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PARP8 NM_024615.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.45

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 (HGNC:):

ACMG classification

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=0.12065524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP8	NM_024615.4	c.802A>T	p.Asn268Tyr	missense_variant	11/26	ENST00000281631.10	NP_078891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP8	ENST00000281631.10	c.802A>T	p.Asn268Tyr	missense_variant	11/26	1	NM_024615.4	ENSP00000281631.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2022

The c.802A>T (p.N268Y) alteration is located in exon 12 (coding exon 11) of the PARP8 gene. This alteration results from a A to T substitution at nucleotide position 802, causing the asparagine (N) at amino acid position 268 to be replaced by a tyrosine (Y). 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	0.11
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.051	T;T;T;.;T
Eigen	Benign	-0.044
Eigen_PC	Benign	0.095
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	.;D;D;D;D
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.;L;L;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.2	N;N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.050	D;D;D;T;T
Sift4G	Uncertain	0.041	D;D;D;D;D
Polyphen		0.96	P;.;P;B;.
Vest4		0.29
MutPred		0.20		Loss of loop (P = 0.0804);.;Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);.;
MVP		0.68
MPC		0.29
ClinPred		0.56	D
GERP RS		4.3
Varity_R		0.045
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-50090105;