chr12-102148403-T-C

Position:

• chr12-102148403-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_017915.5(PARPBP):​c.327T>C​(p.Asp109=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,574,174 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (3 hom.)
• Consequence: PARPBP NM_017915.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0890

Genes affected

PARPBP (HGNC:26074): (PARP1 binding protein) Predicted to enable DNA binding activity. Involved in negative regulation of double-strand break repair via homologous recombination. Located in chromatin and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 12-102148403-T-C is Benign according to our data. Variant chr12-102148403-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2643244.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.089 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARPBP	NM_017915.5	c.327T>C	p.Asp109=	synonymous_variant	3/11	ENST00000327680.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARPBP	ENST00000327680.7	c.327T>C	p.Asp109=	synonymous_variant	3/11	2	NM_017915.5	P1

Frequencies

GnomAD3 genomes AF: 0.00129 AC: 196 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00201

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00134 AC: 333 AN: 248900 Hom.: 1 AF XY: 0.00141 AC XY: 190 AN XY: 134630

Gnomad AFR exome AF: 0.000309

Gnomad AMR exome AF: 0.000888

Gnomad ASJ exome AF: 0.00598

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000332

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.00205

Gnomad OTH exome AF: 0.000825

GnomAD4 exome AF: 0.00165 AC: 2351 AN: 1421906 Hom.: 3 Cov.: 25 AF XY: 0.00163 AC XY: 1154 AN XY: 709616

Gnomad4 AFR exome AF: 0.000428

Gnomad4 AMR exome AF: 0.00107

Gnomad4 ASJ exome AF: 0.00546

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000353

Gnomad4 FIN exome AF: 0.000113

Gnomad4 NFE exome AF: 0.00191

Gnomad4 OTH exome AF: 0.00137

GnomAD4 genome AF: 0.00129 AC: 196 AN: 152268 Hom.: 0 Cov.: 32 AF XY: 0.00105 AC XY: 78 AN XY: 74460

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00202

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00166 Hom.: 1

Bravo AF: 0.00139

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

PARPBP: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.6
DANN	Benign	0.35

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

LitVar

Other links and lift over

dbSNP: rs143799695; hg19: chr12-102542181;