8-143977549-C-A

Variant names:

• chr8-143977549-C-A
• rs200484193
• NM_032789.5:c.3013G>T

Variant summary

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

The NM_032789.5(PARP10):​c.3013G>T​(p.Glu1005*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,414,904 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PARP10 NM_032789.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 0 publications found

Genes affected

PARP10 (HGNC:25895): (poly(ADP-ribose) polymerase family member 10) Poly(ADP-ribose) polymerases (PARPs), such as PARP10, regulate gene transcription by altering chromatin organization by adding ADP-ribose to histones. PARPs can also function as transcriptional cofactors (Yu et al., 2005 [PubMed 15674325]).[supplied by OMIM, Mar 2008]

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_032789.5. 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
	PARP10	NM_032789.5	MANE Select	c.3013G>T	p.Glu1005*	stop_gained	Exon 11 of 11	NP_116178.2	Q53GL7
	PARP10	NM_001317895.2		c.3049G>T	p.Glu1017*	stop_gained	Exon 10 of 10	NP_001304824.1	E9PNI7
	PARP10	NR_134234.2		n.2969G>T		non_coding_transcript_exon	Exon 11 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP10	ENST00000313028.12	TSL:1 MANE Select	c.3013G>T	p.Glu1005*	stop_gained	Exon 11 of 11	ENSP00000325618.7	Q53GL7
	PARP10	ENST00000526007.5	TSL:1	n.1783G>T		non_coding_transcript_exon	Exon 4 of 4
	PARP10	ENST00000527262.5	TSL:1	n.*573G>T		non_coding_transcript_exon	Exon 11 of 11	ENSP00000432733.1	E9PPE7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1414904 Hom.: 0 Cov.: 32 AF XY: 0.00000143 AC XY: 1 AN XY: 699646

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32392

American (AMR) AF: 0.00 AC: 0 AN: 37816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25338

East Asian (EAS) AF: 0.00 AC: 0 AN: 37026

South Asian (SAS) AF: 0.00 AC: 0 AN: 80714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1088378

Other (OTH) AF: 0.00 AC: 0 AN: 58672

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	23
DANN	Benign	0.79
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.031	N
PhyloP100		-2.1
Vest4		0.12
GERP RS		-9.9
Mutation Taster		=63/137	disease causing

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: rs200484193; hg19: chr8-145051717;