ENST00000316562.9:c.-138G>A

Variant names:

• chr20-3888963-G-A
• rs71647825
• ENST00000316562.9:c.-138G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000316562.9(PANK2):​c.-138G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 647,334 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0067 (17 hom., cov: 32)
  • Exomes 𝑓: 0.00072 (2 hom.)
• Consequence: PANK2 ENST00000316562.9 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.400
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 20-3888963-G-A is Benign according to our data. Variant chr20-3888963-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1203236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00669 (1019/152292) while in subpopulation AFR AF = 0.0235 (975/41560). AF 95% confidence interval is 0.0222. There are 17 homozygotes in GnomAd4. There are 487 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

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.-138G>A		5_prime_UTR	Exon 1 of 7	NP_705902.2	Q9BZ23-1
	PANK2	NM_001324192.1		c.-138G>A		5_prime_UTR	Exon 1 of 2	NP_001311121.1
	PANK2	NM_024960.6		c.-246+59G>A		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.-138G>A		5_prime_UTR	Exon 1 of 7	ENSP00000313377.4	Q9BZ23-1
	PANK2	ENST00000495692.5	TSL:3	c.-591G>A		5_prime_UTR	Exon 1 of 6	ENSP00000476745.1	V9GYH1
	PANK2	ENST00000497424.5	TSL:2	c.-246+59G>A		intron	N/A	ENSP00000417609.1	Q9BZ23-2

Frequencies

GnomAD3 genomes AF: 0.00670 AC: 1019 AN: 152174 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

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: 0.0000441

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.000721 AC: 357 AN: 495042 Hom.: 2 Cov.: 6 AF XY: 0.000592 AC XY: 151 AN XY: 254888

African (AFR) AF: 0.0204 AC: 261 AN: 12770

American (AMR) AF: 0.00130 AC: 23 AN: 17686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13114

East Asian (EAS) AF: 0.00 AC: 0 AN: 29812

South Asian (SAS) AF: 0.0000255 AC: 1 AN: 39194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28796

Middle Eastern (MID) AF: 0.000994 AC: 2 AN: 2012

European-Non Finnish (NFE) AF: 0.0000647 AC: 21 AN: 324680

Other (OTH) AF: 0.00182 AC: 49 AN: 26978

GnomAD4 genome AF: 0.00669 AC: 1019 AN: 152292 Hom.: 17 Cov.: 32 AF XY: 0.00654 AC XY: 487 AN XY: 74470

African (AFR) AF: 0.0235 AC: 975 AN: 41560

American (AMR) AF: 0.00203 AC: 31 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68026

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00387 Hom.: 1

Bravo AF: 0.00749

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	4.0
DANN	Benign	0.92
PhyloP100		-0.40
PromoterAI		0.027	Neutral
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: rs71647825; hg19: chr20-3869610;