rs1043502

Variant names:

• chr1-20651255-T-G
• rs1043502
• NM_032409.3:c.*564T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032409.3(PINK1):​c.*564T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 165,700 control chromosomes in the GnomAD database, including 6,601 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6000 hom., cov: 35)
  • Exomes 𝑓: 0.27 (601 hom.)
• Consequence: PINK1 NM_032409.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.229
• Publications: 18 publications found

Genes affected

PINK1 (HGNC:14581): (PTEN induced kinase 1) This gene encodes a serine/threonine protein kinase that localizes to mitochondria. It is thought to protect cells from stress-induced mitochondrial dysfunction. Mutations in this gene cause one form of autosomal recessive early-onset Parkinson disease. [provided by RefSeq, Jul 2008]

PINK1-AS (HGNC:38872): (PINK1 antisense RNA)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-20651255-T-G is Benign according to our data. Variant chr1-20651255-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 295024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032409.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PINK1	NM_032409.3	MANE Select	c.*564T>G		3_prime_UTR	Exon 8 of 8	NP_115785.1	Q9BXM7-1
	PINK1-AS	NR_046507.1		n.939A>C		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PINK1	ENST00000321556.5	TSL:1 MANE Select	c.*564T>G		3_prime_UTR	Exon 8 of 8	ENSP00000364204.3	Q9BXM7-1
	PINK1	ENST00000878749.1		c.*564T>G		3_prime_UTR	Exon 8 of 8	ENSP00000548808.1
	PINK1	ENST00000878743.1		c.*564T>G		3_prime_UTR	Exon 8 of 8	ENSP00000548802.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42098 AN: 151728 Hom.: 5997 Cov.: 35

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 0.266 AC: 3692 AN: 13870 Hom.: 601 Cov.: 0 AF XY: 0.273 AC XY: 1930 AN XY: 7072

African (AFR) AF: 0.219 AC: 63 AN: 288

American (AMR) AF: 0.229 AC: 650 AN: 2840

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 13 AN: 106

East Asian (EAS) AF: 0.323 AC: 370 AN: 1144

South Asian (SAS) AF: 0.350 AC: 526 AN: 1502

European-Finnish (FIN) AF: 0.275 AC: 66 AN: 240

Middle Eastern (MID) AF: 0.286 AC: 4 AN: 14

European-Non Finnish (NFE) AF: 0.257 AC: 1839 AN: 7144

Other (OTH) AF: 0.272 AC: 161 AN: 592

GnomAD4 genome AF: 0.277 AC: 42118 AN: 151830 Hom.: 6000 Cov.: 35 AF XY: 0.281 AC XY: 20854 AN XY: 74198

African (AFR) AF: 0.263 AC: 10856 AN: 41218

American (AMR) AF: 0.235 AC: 3590 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 683 AN: 3468

East Asian (EAS) AF: 0.349 AC: 1799 AN: 5156

South Asian (SAS) AF: 0.384 AC: 1842 AN: 4792

European-Finnish (FIN) AF: 0.352 AC: 3726 AN: 10590

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.275 AC: 18726 AN: 68020

Other (OTH) AF: 0.267 AC: 561 AN: 2100

Alfa AF: 0.270 Hom.: 3732

Bravo AF: 0.268

Asia WGS AF: 0.314 AC: 1091 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal recessive early-onset Parkinson disease 6 (1)
-	-	1	Congenital disorder of glycosylation (1)
-	-	1	Parkinson Disease, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.45
PhyloP100		-0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1043502; hg19: chr1-20977748;