Genetic Variant PARP10:p.Glu1005Lys (chr8-143977549-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_032789.5(PARP10):c.3013G>A(p.Glu1005Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,567,156 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

PARP10
NM_032789.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.05

Publications

2 publications found

Variant links:

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]

PARP10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044091046).

BP6

Variant 8-143977549-C-T is Benign according to our data. Variant chr8-143977549-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2366729.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PARP10	NM_032789.5	MANE Select	c.3013G>A	p.Glu1005Lys	missense	Exon 11 of 11	NP_116178.2	Q53GL7
PARP10	NM_001317895.2		c.3049G>A	p.Glu1017Lys	missense	Exon 10 of 10	NP_001304824.1	E9PNI7
PARP10	NR_134234.2		n.2969G>A		non_coding_transcript_exon	Exon 11 of 11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PARP10	ENST00000313028.12	TSL:1 MANE Select	c.3013G>A	p.Glu1005Lys	missense	Exon 11 of 11	ENSP00000325618.7	Q53GL7
PARP10	ENST00000526007.5	TSL:1	n.1783G>A		non_coding_transcript_exon	Exon 4 of 4
PARP10	ENST00000527262.5	TSL:1	n.*573G>A		non_coding_transcript_exon	Exon 11 of 11	ENSP00000432733.1	E9PPE7

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000440

AC:

AN:

172904

AF XY:

0.000454

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00325

Gnomad EAS exome

AF:

0.00197

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000101

Gnomad OTH exome

AF:

0.000428

GnomAD4 exome

AF:

0.000152

AC:

215

AN:

1414904

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

124

AN XY:

699646

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32392

American (AMR)

AF:

0.00

AC:

AN:

37816

Ashkenazi Jewish (ASJ)

AF:

0.00343

AC:

AN:

25338

East Asian (EAS)

AF:

0.000864

AC:

AN:

37026

South Asian (SAS)

AF:

0.000496

AC:

AN:

80714

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48856

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.0000119

AC:

AN:

1088378

Other (OTH)

AF:

0.000716

AC:

AN:

58672

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000243

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41546

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3472

East Asian (EAS)

AF:

0.00290

AC:

AN:

5172

South Asian (SAS)

AF:

0.000622

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000304

Hom.:

Bravo

AF:

0.000230

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000235

AC:

ExAC

AF:

0.000246

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.010

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.00083

Eigen

Benign

-2.5

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.64

M_CAP

Benign

0.0048

MetaRNN

Benign

0.0044

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.70

PhyloP100

-2.1

PrimateAI

Benign

0.32

PROVEAN

Benign

1.7

REVEL

Benign

0.033

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.063

MVP

0.28

MPC

0.73

ClinPred

0.023

GERP RS

-9.9

Varity_R

0.22

gMVP

0.79

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over