20-3889124-C-T

Variant names:

• chr20-3889124-C-T
• rs1216238658
• ENST00000316562.9:c.24C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_153638.4(PANK2):​c.24C>T​(p.His8His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 1,553,322 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PANK2 NM_153638.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.822
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 20-3889124-C-T is Benign according to our data. Variant chr20-3889124-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2917850.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.822 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.24C>T	p.His8His	synonymous	Exon 1 of 7	NP_705902.2	Q9BZ23-1
	PANK2	NM_001324192.1		c.24C>T	p.His8His	synonymous	Exon 1 of 2	NP_001311121.1
	PANK2	NM_024960.6		c.-246+220C>T		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.24C>T	p.His8His	synonymous	Exon 1 of 7	ENSP00000313377.4	Q9BZ23-1
	PANK2	ENST00000497424.5	TSL:2	c.-246+220C>T		intron	N/A	ENSP00000417609.1	Q9BZ23-2
	PANK2	ENST00000495692.5	TSL:3	c.-538+108C>T		intron	N/A	ENSP00000476745.1	V9GYH1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1401114 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 691316

African (AFR) AF: 0.0000315 AC: 1 AN: 31774

American (AMR) AF: 0.00 AC: 0 AN: 36052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25134

East Asian (EAS) AF: 0.00 AC: 0 AN: 36076

South Asian (SAS) AF: 0.00 AC: 0 AN: 79554

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5346

European-Non Finnish (NFE) AF: 9.26e-7 AC: 1 AN: 1079954

Other (OTH) AF: 0.00 AC: 0 AN: 58010

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74362

African (AFR) AF: 0.0000241 AC: 1 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.92
PhyloP100		0.82
PromoterAI		-0.071	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: rs1216238658; hg19: chr20-3869771;