6-162727551-C-T

Position:

• chr6-162727551-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004562.3(PRKN):​c.7+111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 1,213,244 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (45 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (21 hom.)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0760

Genes affected

PRKN (HGNC:8607): (parkin RBR E3 ubiquitin protein ligase) The precise function of this gene is unknown; however, the encoded protein is a component of a multiprotein E3 ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. Mutations in this gene are known to cause Parkinson disease and autosomal recessive juvenile Parkinson disease. Alternative splicing of this gene produces multiple transcript variants encoding distinct isoforms. Additional splice variants of this gene have been described but currently lack transcript support. [provided by RefSeq, Jul 2008]

PACRG (HGNC:19152): (parkin coregulated) This gene encodes a protein that is conserved across metazoans. In vertebrates, this gene is linked in a head-to-head arrangement with the adjacent parkin gene, which is associated with autosomal recessive juvenile Parkinson's disease. These genes are co-regulated in various tissues and they share a bi-directional promoter. Both genes are associated with susceptibility to leprosy. The parkin co-regulated gene protein forms a large molecular complex with chaperones, including heat shock proteins 70 and 90, and chaperonin components. This protein is also a component of Lewy bodies in Parkinson's disease patients, and it suppresses unfolded Pael receptor-induced neuronal cell death. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PRKN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 6-162727551-C-T is Benign according to our data. Variant chr6-162727551-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1220094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0129 (1970/152204) while in subpopulation AFR AF= 0.0444 (1845/41570). AF 95% confidence interval is 0.0427. There are 45 homozygotes in gnomad4. There are 901 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKN	NM_004562.3	c.7+111G>A		intron_variant		ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.7+111G>A		intron_variant		1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1968 AN: 152092 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.0444

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.00860

GnomAD4 exome AF: 0.00141 AC: 1499 AN: 1061040 Hom.: 21 AF XY: 0.00119 AC XY: 634 AN XY: 534920

Gnomad4 AFR exome AF: 0.0438

Gnomad4 AMR exome AF: 0.00381

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000983

Gnomad4 FIN exome AF: 0.0000234

Gnomad4 NFE exome AF: 0.000175

Gnomad4 OTH exome AF: 0.00386

GnomAD4 genome AF: 0.0129 AC: 1970 AN: 152204 Hom.: 45 Cov.: 32 AF XY: 0.0121 AC XY: 901 AN XY: 74418

Gnomad4 AFR AF: 0.0444

Gnomad4 AMR AF: 0.00543

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000324

Gnomad4 OTH AF: 0.00852

Alfa AF: 0.00868 Hom.: 2

Bravo AF: 0.0154

Asia WGS AF: 0.00607 AC: 22 AN: 3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.3
DANN	Benign	0.93

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: rs114231735; hg19: chr6-163148583;