chr20-3889145-G-C

Variant names:

• chr20-3889145-G-C
• rs764726817
• ENST00000316562.9:c.45G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_153638.4(PANK2):​c.45G>C​(p.Ala15Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,423,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A15A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PANK2 NM_153638.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.692
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=0.692 with no splicing effect.

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.45G>C	p.Ala15Ala	synonymous	Exon 1 of 7	NP_705902.2	Q9BZ23-1
	PANK2	NM_001324192.1		c.45G>C	p.Ala15Ala	synonymous	Exon 1 of 2	NP_001311121.1
	PANK2	NM_024960.6		c.-246+241G>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.45G>C	p.Ala15Ala	synonymous	Exon 1 of 7	ENSP00000313377.4	Q9BZ23-1
	PANK2	ENST00000497424.5	TSL:2	c.-246+241G>C		intron	N/A	ENSP00000417609.1	Q9BZ23-2
	PANK2	ENST00000495692.5	TSL:3	c.-538+129G>C		intron	N/A	ENSP00000476745.1	V9GYH1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1423538 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 704608

African (AFR) AF: 0.00 AC: 0 AN: 32490

American (AMR) AF: 0.00 AC: 0 AN: 39234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25378

East Asian (EAS) AF: 0.00 AC: 0 AN: 37582

South Asian (SAS) AF: 0.00 AC: 0 AN: 81356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1092362

Other (OTH) AF: 0.00 AC: 0 AN: 58850

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.60
PhyloP100		0.69
PromoterAI		-0.23	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: rs764726817; hg19: chr20-3869792;