rs148036492

Variant names:

• chr20-3889237-A-G
• rs148036492
• ENST00000316562.9:c.137A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-3889237-A-G
• chr20-3889237-A-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The ENST00000316562.9(PANK2):​c.137A>G​(p.Asp46Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D46V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PANK2 ENST00000316562.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871
• Publications: 9 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
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 41 curated pathogenic missense variants (we use a threshold of 10). The gene has 11 curated benign missense variants. Gene score misZ: 0.17856 (below the threshold of 3.09). Trascript score misZ: -1.1034 (below the threshold of 3.09). GenCC associations: The gene is linked to pantothenate kinase-associated neurodegeneration.
• BP4: Computational evidence support a benign effect (MetaRNN=0.042028874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANK2	NM_001386393.1	c.-194A>G		upstream_gene_variant		ENST00000610179.7	NP_001373322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANK2	ENST00000610179.7	c.-194A>G		upstream_gene_variant		1	NM_001386393.1	ENSP00000477429.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460980 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726656

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 85898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111722

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.0069	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	3.6
DANN	Benign	0.61
DEOGEN2	Benign	0.18	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.085	D
MetaRNN	Benign	0.042	T
MetaSVM	Uncertain	0.037	D
MutationAssessor	Benign	0.0	N
PhyloP100		-0.87
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	0.81	T
Polyphen		0.0	B
Vest4		0.092
MutPred		0.17		Gain of sheet (P = 0.0266);
MVP		0.64
MPC		0.59
ClinPred		0.087	T
GERP RS		-3.8
PromoterAI		-0.030	Neutral
Varity_R		0.034
gMVP		0.021
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs148036492; hg19: chr20-3869884;