NM_024615.4:c.365C>T

Variant names:

• chr5-50761840-C-T
• rs762080636
• NM_024615.4:c.365C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024615.4(PARP8):​c.365C>T​(p.Thr122Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,446,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PARP8 NM_024615.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.69
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22953111).

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.365C>T	p.Thr122Ile	missense	Exon 6 of 26	NP_078891.2
	PARP8	NM_001427055.1		c.488C>T	p.Thr163Ile	missense	Exon 7 of 27	NP_001413984.1
	PARP8	NM_001178055.2		c.365C>T	p.Thr122Ile	missense	Exon 7 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.365C>T	p.Thr122Ile	missense	Exon 6 of 26	ENSP00000281631.4	Q8N3A8-1
	PARP8	ENST00000505697.6	TSL:1	c.365C>T	p.Thr122Ile	missense	Exon 7 of 27	ENSP00000422217.2	Q8N3A8-1
	PARP8	ENST00000514067.6	TSL:1	c.365C>T	p.Thr122Ile	missense	Exon 6 of 25	ENSP00000424814.2	Q8N3A8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000410 AC: 1 AN: 244044 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1446054 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 719722

African (AFR) AF: 0.00 AC: 0 AN: 33000

American (AMR) AF: 0.00 AC: 0 AN: 43402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25886

East Asian (EAS) AF: 0.00 AC: 0 AN: 38950

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101356

Other (OTH) AF: 0.00 AC: 0 AN: 59806

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.080
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.7
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.16
Sift	Uncertain	0.023	D
Sift4G	Benign	0.36	T
Polyphen		0.079	B
Vest4		0.47
MutPred		0.21		Loss of glycosylation at T122 (P = 0.0295)
MVP		0.64
MPC		0.21
ClinPred		0.40	T
GERP RS		5.5
Varity_R		0.15
gMVP		0.18
Mutation Taster		=247/53	polymorphism

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

Other links and lift over

dbSNP: rs762080636; hg19: chr5-50057674;