rs2078073

Variant names:

• chr1-20651363-T-C
• rs2078073
• NM_032409.3:c.*672T>C

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.*672T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 154,648 control chromosomes in the GnomAD database, including 6,148 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 (6024 hom., cov: 34)
  • Exomes 𝑓: 0.29 (124 hom.)
• Consequence: PINK1 NM_032409.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.463
• Publications: 8 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=-0.84).
• BP6: Variant 1-20651363-T-C is Benign according to our data. Variant chr1-20651363-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 295030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.367 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.*672T>C		3_prime_UTR	Exon 8 of 8	NP_115785.1	Q9BXM7-1
	PINK1-AS	NR_046507.1		n.831A>G		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.*672T>C		3_prime_UTR	Exon 8 of 8	ENSP00000364204.3	Q9BXM7-1
	PINK1	ENST00000878743.1		c.*672T>C		3_prime_UTR	Exon 8 of 8	ENSP00000548802.1
	PINK1	ENST00000945624.1		c.*672T>C		3_prime_UTR	Exon 8 of 8	ENSP00000615683.1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42219 AN: 151986 Hom.: 6021 Cov.: 34

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 0.287 AC: 729 AN: 2544 Hom.: 124 Cov.: 0 AF XY: 0.296 AC XY: 372 AN XY: 1256

African (AFR) AF: 0.500 AC: 3 AN: 6

American (AMR) AF: 0.266 AC: 144 AN: 542

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 1 AN: 6

East Asian (EAS) AF: 0.333 AC: 18 AN: 54

South Asian (SAS) AF: 0.419 AC: 62 AN: 148

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.278 AC: 471 AN: 1692

Other (OTH) AF: 0.289 AC: 26 AN: 90

GnomAD4 genome AF: 0.278 AC: 42239 AN: 152104 Hom.: 6024 Cov.: 34 AF XY: 0.281 AC XY: 20910 AN XY: 74364

African (AFR) AF: 0.262 AC: 10892 AN: 41496

American (AMR) AF: 0.236 AC: 3599 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 683 AN: 3470

East Asian (EAS) AF: 0.359 AC: 1858 AN: 5180

South Asian (SAS) AF: 0.381 AC: 1838 AN: 4818

European-Finnish (FIN) AF: 0.353 AC: 3730 AN: 10568

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18740 AN: 67978

Other (OTH) AF: 0.266 AC: 562 AN: 2110

Alfa AF: 0.271 Hom.: 4025

Bravo AF: 0.269

Asia WGS AF: 0.327 AC: 1134 AN: 3478

ClinVar

ClinVar submissions

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	-0.84
CADD	Benign	0.91
DANN	Benign	0.66
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism

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: rs2078073; hg19: chr1-20977856;