Variant 7-140026320-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022750.4(PARP12):c.1657G>A(p.Gly553Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000484 in 1,612,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

PARP12
NM_022750.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73

Variant links:

Genes affected

PARP12 (HGNC:21919): (poly(ADP-ribose) polymerase family member 12) Enables protein ADP-ribosylase activity. Involved in protein auto-ADP-ribosylation and protein mono-ADP-ribosylation. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PARP12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1576064).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP12	NM_022750.4 link	c.1657G>A	p.Gly553Arg	missense_variant	11/12	ENST00000263549.8	NP_073587.1	Q9H0J9A4D1T0
PARP12	XM_047420739.1 link	c.1762G>A	p.Gly588Arg	missense_variant	11/12		XP_047276695.1
PARP12	XM_047420741.1 link	c.1526G>A	p.Arg509Gln	missense_variant	10/10		XP_047276697.1
PARP12	NR_130117.2 link	n.1619G>A		non_coding_transcript_exon_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP12	ENST00000263549.8 link	c.1657G>A	p.Gly553Arg	missense_variant	11/12	1	NM_022750.4	ENSP00000263549.3		Q9H0J9

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000641

AC:

AN:

249490

Hom.:

AF XY:

0.0000593

AC XY:

AN XY:

135000

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000793

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000404

AC:

AN:

1459950

Hom.:

Cov.:

AF XY:

0.0000372

AC XY:

AN XY:

726370

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000423

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000125

AC:

AN:

152374

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.000264

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000793

Hom.:

Bravo

AF:

0.000102

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2022

The c.1657G>A (p.G553R) alteration is located in exon 11 (coding exon 11) of the PARP12 gene. This alteration results from a G to A substitution at nucleotide position 1657, causing the glycine (G) at amino acid position 553 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

0.044

Eigen_PC

Benign

-0.0028

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.73

M_CAP

Benign

0.043

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.50

MutationAssessor

Uncertain

2.6

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.14

Sift

Benign

0.086

Sift4G

Benign

0.15

Polyphen

1.0

Vest4

0.31

MutPred

0.50

Loss of ubiquitination at K555 (P = 0.0193);

MVP

0.47

MPC

0.89

ClinPred

0.98

GERP RS

4.8

Varity_R

0.50

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over