rs1043424

Variant names:

• chr1-20650507-A-C
• rs1043424
• NM_032409.3:c.1562A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-20650507-A-C
• chr1-20650507-A-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.1562A>C​(p.Asn521Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,613,924 control chromosomes in the GnomAD database, including 66,988 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (5989 hom., cov: 33)
  • Exomes 𝑓: 0.29 (60999 hom.)
• Consequence: PINK1 NM_032409.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: 0.617
• Publications: 81 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 (MetaRNN=0.0024134517).
• BP6: Variant 1-20650507-A-C is Benign according to our data. Variant chr1-20650507-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 295006.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.1562A>C	p.Asn521Thr	missense	Exon 8 of 8	NP_115785.1	Q9BXM7-1
	PINK1-AS	NR_046507.1		n.1687T>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.1562A>C	p.Asn521Thr	missense	Exon 8 of 8	ENSP00000364204.3	Q9BXM7-1
	PINK1	ENST00000878749.1		c.1592A>C	p.Asn531Thr	missense	Exon 8 of 8	ENSP00000548808.1
	PINK1	ENST00000878743.1		c.1580A>C	p.Asn527Thr	missense	Exon 8 of 8	ENSP00000548802.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42053 AN: 151968 Hom.: 5986 Cov.: 33

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.268

GnomAD2 exomes AF: 0.292 AC: 73476 AN: 251378 AF XY: 0.298

Gnomad AFR exome AF: 0.269

Gnomad AMR exome AF: 0.233

Gnomad ASJ exome AF: 0.192

Gnomad EAS exome AF: 0.352

Gnomad FIN exome AF: 0.369

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.270

GnomAD4 exome AF: 0.286 AC: 417477 AN: 1461838 Hom.: 60999 Cov.: 57 AF XY: 0.288 AC XY: 209526 AN XY: 727232

African (AFR) AF: 0.258 AC: 8632 AN: 33474

American (AMR) AF: 0.229 AC: 10261 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 5193 AN: 26136

East Asian (EAS) AF: 0.334 AC: 13263 AN: 39698

South Asian (SAS) AF: 0.376 AC: 32423 AN: 86254

European-Finnish (FIN) AF: 0.365 AC: 19505 AN: 53414

Middle Eastern (MID) AF: 0.218 AC: 1259 AN: 5768

European-Non Finnish (NFE) AF: 0.278 AC: 309674 AN: 1111988

Other (OTH) AF: 0.286 AC: 17267 AN: 60390

GnomAD4 genome AF: 0.277 AC: 42073 AN: 152086 Hom.: 5989 Cov.: 33 AF XY: 0.280 AC XY: 20830 AN XY: 74344

African (AFR) AF: 0.261 AC: 10839 AN: 41478

American (AMR) AF: 0.234 AC: 3582 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 683 AN: 3472

East Asian (EAS) AF: 0.347 AC: 1788 AN: 5152

South Asian (SAS) AF: 0.382 AC: 1838 AN: 4816

European-Finnish (FIN) AF: 0.352 AC: 3724 AN: 10576

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

European-Non Finnish (NFE) AF: 0.275 AC: 18723 AN: 67990

Other (OTH) AF: 0.265 AC: 560 AN: 2112

Alfa AF: 0.271 Hom.: 23292

Bravo AF: 0.268

TwinsUK AF: 0.271 AC: 1005

ALSPAC AF: 0.284 AC: 1094

ESP6500AA AF: 0.268 AC: 1179

ESP6500EA AF: 0.271 AC: 2333

ExAC AF: 0.297 AC: 36089

Asia WGS AF: 0.314 AC: 1092 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	4	Autosomal recessive early-onset Parkinson disease 6 (4)
-	-	2	not provided (2)
-	-	1	Congenital disorder of glycosylation (1)
-	-	1	Parkinson Disease, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.62
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.040
Sift	Benign	0.25	T
Sift4G	Benign	0.41	T
Polyphen		0.022	B
Vest4		0.10
MPC		0.18
ClinPred		0.0024	T
GERP RS		1.6
Varity_R		0.061
gMVP		0.090
Mutation Taster		=96/4	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: rs1043424; hg19: chr1-20977000; COSMIC: COSV58630745; COSMIC: COSV58630745;