20-3889079-G-C

Variant names:

• chr20-3889079-G-C
• rs199787176
• ENST00000316562.9:c.-22G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_153638.4(PANK2):​c.-22G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00328 in 1,520,538 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (24 hom.)
• Consequence: PANK2 NM_153638.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0650
• Publications: 1 publications found

Genes affected

PANK2 (HGNC:15894): (pantothenate kinase 2) This gene encodes a protein belonging to the pantothenate kinase family and is the only member of that family to be expressed in mitochondria. Pantothenate kinase is a key regulatory enzyme in the biosynthesis of coenzyme A (CoA) in bacteria and mammalian cells. It catalyzes the first committed step in the universal biosynthetic pathway leading to CoA and is itself subject to regulation through feedback inhibition by acyl CoA species. Mutations in this gene are associated with HARP syndrome and pantothenate kinase-associated neurodegeneration (PKAN), formerly Hallervorden-Spatz syndrome. Alternative splicing, involving the use of alternate first exons, results in multiple transcripts encoding different isoforms. [provided by RefSeq, Jul 2008]

PANK2-AS1 (HGNC:40732): (PANK2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 20-3889079-G-C is Benign according to our data. Variant chr20-3889079-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1194321.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00265 (403/152158) while in subpopulation EAS AF = 0.033 (170/5146). AF 95% confidence interval is 0.029. There are 1 homozygotes in GnomAd4. There are 187 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 24 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153638.4. 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
	PANK2	NM_153638.4		c.-22G>C		5_prime_UTR	Exon 1 of 7	NP_705902.2	Q9BZ23-1
	PANK2	NM_001324192.1		c.-22G>C		5_prime_UTR	Exon 1 of 2	NP_001311121.1
	PANK2	NM_024960.6		c.-246+175G>C		intron	N/A	NP_079236.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANK2	ENST00000316562.9	TSL:1	c.-22G>C		5_prime_UTR	Exon 1 of 7	ENSP00000313377.4	Q9BZ23-1
	PANK2	ENST00000497424.5	TSL:2	c.-246+175G>C		intron	N/A	ENSP00000417609.1	Q9BZ23-2
	PANK2	ENST00000495692.5	TSL:3	c.-538+63G>C		intron	N/A	ENSP00000476745.1	V9GYH1

Frequencies

GnomAD3 genomes AF: 0.00264 AC: 402 AN: 152040 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000942

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0328

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00244

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00395 AC: 517 AN: 131030 AF XY: 0.00379

Gnomad AFR exome AF: 0.000550

Gnomad AMR exome AF: 0.000812

Gnomad ASJ exome AF: 0.000316

Gnomad EAS exome AF: 0.0325

Gnomad FIN exome AF: 0.000316

Gnomad NFE exome AF: 0.00249

Gnomad OTH exome AF: 0.00234

GnomAD4 exome AF: 0.00335 AC: 4580 AN: 1368380 Hom.: 24 Cov.: 29 AF XY: 0.00326 AC XY: 2193 AN XY: 672588

African (AFR) AF: 0.000449 AC: 14 AN: 31160

American (AMR) AF: 0.000958 AC: 33 AN: 34436

Ashkenazi Jewish (ASJ) AF: 0.000430 AC: 10 AN: 23236

East Asian (EAS) AF: 0.0252 AC: 896 AN: 35554

South Asian (SAS) AF: 0.000504 AC: 38 AN: 75462

European-Finnish (FIN) AF: 0.000485 AC: 22 AN: 45354

Middle Eastern (MID) AF: 0.000748 AC: 3 AN: 4010

European-Non Finnish (NFE) AF: 0.00312 AC: 3315 AN: 1062486

Other (OTH) AF: 0.00439 AC: 249 AN: 56682

GnomAD4 genome AF: 0.00265 AC: 403 AN: 152158 Hom.: 1 Cov.: 32 AF XY: 0.00251 AC XY: 187 AN XY: 74406

African (AFR) AF: 0.000939 AC: 39 AN: 41528

American (AMR) AF: 0.000719 AC: 11 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0330 AC: 170 AN: 5146

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4828

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00244 AC: 166 AN: 67974

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.000719 Hom.: 1

Bravo AF: 0.00265

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.8
DANN	Benign	0.37
PhyloP100		0.065
PromoterAI		0.072	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs199787176; hg19: chr20-3869726;