8-143982984-C-A

Variant names:

• chr8-143982984-C-A
• rs371846207
• NM_032789.5:c.2504G>T

Variant summary

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

The NM_032789.5(PARP10):​c.2504G>T​(p.Arg835Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. R835Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PARP10 NM_032789.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.117142886).

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.2504G>T	p.Arg835Leu	missense	Exon 9 of 11	NP_116178.2	Q53GL7
	PARP10	NM_001317895.2		c.2540G>T	p.Arg847Leu	missense	Exon 8 of 10	NP_001304824.1	E9PNI7
	PARP10	NR_134234.2		n.2460G>T		non_coding_transcript_exon	Exon 9 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP10	ENST00000313028.12	TSL:1 MANE Select	c.2504G>T	p.Arg835Leu	missense	Exon 9 of 11	ENSP00000325618.7	Q53GL7
	PARP10	ENST00000526007.5	TSL:1	n.1274G>T		non_coding_transcript_exon	Exon 2 of 4
	PARP10	ENST00000527262.5	TSL:1	n.*64G>T		non_coding_transcript_exon	Exon 9 of 11	ENSP00000432733.1	E9PPE7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461614 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727128

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.6
DANN	Benign	0.97
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		-1.7
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.019
Sift	Uncertain	0.022	D
Sift4G	Benign	0.12	T
Polyphen		0.056	B
Vest4		0.31
MutPred		0.56		Loss of MoRF binding (P = 0.018)
MVP		0.27
MPC		0.87
ClinPred		0.14	T
GERP RS		-4.6
Varity_R		0.22
gMVP		0.43
Mutation Taster		=74/26	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: rs371846207; hg19: chr8-145057152;