5-50667121-G-T

Variant names:

• chr5-50667121-G-T
• rs748506179
• NM_024615.4:c.26G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024615.4(PARP8):​c.26G>T​(p.Arg9Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,108 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R9Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PARP8 NM_024615.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.34
• Publications: 0 publications found

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]

ENSG00000289056 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024615.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP8	NM_024615.4	MANE Select	c.26G>T	p.Arg9Leu	missense	Exon 1 of 26	NP_078891.2
	PARP8	NM_001427055.1		c.149G>T	p.Arg50Leu	missense	Exon 2 of 27	NP_001413984.1
	PARP8	NM_001178055.2		c.26G>T	p.Arg9Leu	missense	Exon 2 of 27	NP_001171526.1	Q8N3A8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP8	ENST00000281631.10	TSL:1 MANE Select	c.26G>T	p.Arg9Leu	missense	Exon 1 of 26	ENSP00000281631.4	Q8N3A8-1
	PARP8	ENST00000505697.6	TSL:1	c.26G>T	p.Arg9Leu	missense	Exon 2 of 27	ENSP00000422217.2	Q8N3A8-1
	PARP8	ENST00000514067.6	TSL:1	c.26G>T	p.Arg9Leu	missense	Exon 1 of 25	ENSP00000424814.2	Q8N3A8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444108 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 718794

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111724

Other (OTH) AF: 0.00 AC: 0 AN: 60106

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	26
DANN	Uncertain	0.97
DEOGEN2	Benign	0.040	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.071	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.0	N
PhyloP100		7.3
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.93	N
REVEL	Uncertain	0.53
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.020	B
Vest4		0.78
MutPred		0.67		Loss of disorder (P = 0.0084)
MVP		0.40
MPC		0.30
ClinPred		0.93	D
GERP RS		4.2
PromoterAI		-0.087	Neutral
Varity_R		0.50
gMVP		0.60
Mutation Taster		=57/43	polymorphism

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

Other links and lift over

dbSNP: rs748506179; hg19: chr5-49962955;