19-49861087-G-GC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000636840.1(PNKP):c.59+520_59+521insG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0378 in 677,362 control chromosomes in the GnomAD database, including 914 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (93 hom., cov: 32)
  • Exomes 𝑓: 0.041 (821 hom.)
• Consequence: PNKP ENST00000636840.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.500

Genes affected

PNKP (HGNC:9154): (polynucleotide kinase 3'-phosphatase) This locus represents a gene involved in DNA repair. In response to ionizing radiation or oxidative damage, the protein encoded by this locus catalyzes 5' phosphorylation and 3' dephosphorylation of nucleic acids. Mutations at this locus have been associated with microcephaly, seizures, and developmental delay.[provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 19-49861087-G-GC is Benign according to our data. Variant chr19-49861087-G-GC is described in ClinVar as [Likely_benign]. Clinvar id is 1208797.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNKP	ENST00000636840.1	c.59+520_59+521insG		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3988 AN: 152154 Hom.: 90 Cov.: 32

Gnomad AFR AF: 0.00678

Gnomad AMI AF: 0.0650

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.0591

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0192

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.0282

GnomAD4 exome AF: 0.0412 AC: 21635 AN: 525090 Hom.: 821 AF XY: 0.0453 AC XY: 12819 AN XY: 282670

Gnomad4 AFR exome AF: 0.00748

Gnomad4 AMR exome AF: 0.0118

Gnomad4 ASJ exome AF: 0.0435

Gnomad4 EAS exome AF: 0.0727

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.0233

Gnomad4 NFE exome AF: 0.0312

Gnomad4 OTH exome AF: 0.0353

GnomAD4 genome AF: 0.0262 AC: 3996 AN: 152272 Hom.: 93 Cov.: 32 AF XY: 0.0265 AC XY: 1974 AN XY: 74450

Gnomad4 AFR AF: 0.00676

Gnomad4 AMR AF: 0.0181

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.0592

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0192

Gnomad4 NFE AF: 0.0301

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0239 Hom.: 3

Bravo AF: 0.0230

Asia WGS AF: 0.122 AC: 422 AN: 3478

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

GeneDx

Jun 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3739210; hg19: chr19-50364344;