ENST00000316562.9:c.54A>G

Variant names:

• chr20-3889154-A-G
• rs886056650
• ENST00000316562.9:c.54A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6 BP7

The ENST00000316562.9(PANK2):​c.54A>G​(p.Ser18Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000486 in 1,439,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: PANK2 ENST00000316562.9 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.153
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 20-3889154-A-G is Benign according to our data. Variant chr20-3889154-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 338357.
• BP7: Synonymous conserved (PhyloP=0.153 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000316562.9. 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.54A>G	p.Ser18Ser	synonymous	Exon 1 of 7	NP_705902.2	Q9BZ23-1
	PANK2	NM_001324192.1		c.54A>G	p.Ser18Ser	synonymous	Exon 1 of 2	NP_001311121.1
	PANK2	NM_024960.6		c.-246+250A>G		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.54A>G	p.Ser18Ser	synonymous	Exon 1 of 7	ENSP00000313377.4	Q9BZ23-1
	PANK2	ENST00000497424.5	TSL:2	c.-246+250A>G		intron	N/A	ENSP00000417609.1	Q9BZ23-2
	PANK2	ENST00000495692.5	TSL:3	c.-538+138A>G		intron	N/A	ENSP00000476745.1	V9GYH1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000469 AC: 1 AN: 213054 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000107

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000486 AC: 7 AN: 1439492 Hom.: 0 Cov.: 31 AF XY: 0.00000280 AC XY: 2 AN XY: 713894

African (AFR) AF: 0.00 AC: 0 AN: 32968

American (AMR) AF: 0.00 AC: 0 AN: 41736

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25578

East Asian (EAS) AF: 0.00 AC: 0 AN: 38554

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51702

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00000545 AC: 6 AN: 1101050

Other (OTH) AF: 0.00 AC: 0 AN: 59466

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	Pigmentary pallidal degeneration (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		0.15
PromoterAI		0.025	Neutral

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: rs886056650; hg19: chr20-3869801;