20-3889155-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The ENST00000316562.9(PANK2):c.55C>T(p.Leu19Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000486 in 1,440,946 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000049 ( 0 hom. )
Consequence
PANK2
ENST00000316562.9 missense
ENST00000316562.9 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 1.56
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.22484428).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PANK2-AS1 | XR_001754478.3 | n.19G>A | non_coding_transcript_exon_variant | 1/2 | ||||
PANK2 | NM_153638.4 | c.55C>T | p.Leu19Phe | missense_variant | 1/7 | NP_705902.2 | ||
PANK2 | NM_001324192.1 | c.55C>T | p.Leu19Phe | missense_variant | 1/2 | NP_001311121.1 | ||
PANK2 | NM_024960.6 | c.-246+251C>T | intron_variant | NP_079236.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PANK2 | ENST00000316562.9 | c.55C>T | p.Leu19Phe | missense_variant | 1/7 | 1 | ENSP00000313377 | A2 | ||
PANK2-AS1 | ENST00000702266.1 | n.19G>A | non_coding_transcript_exon_variant | 1/1 | ||||||
PANK2 | ENST00000495692.5 | c.-538+139C>T | intron_variant | 3 | ENSP00000476745 | |||||
PANK2 | ENST00000497424.5 | c.-246+251C>T | intron_variant | 2 | ENSP00000417609 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.00000465 AC: 1AN: 215280Hom.: 0 AF XY: 0.00000860 AC XY: 1AN XY: 116298
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GnomAD4 exome AF: 0.00000486 AC: 7AN: 1440946Hom.: 0 Cov.: 31 AF XY: 0.00000420 AC XY: 3AN XY: 714744
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GnomAD4 genome Cov.: 33
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33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Pigmentary pallidal degeneration Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 11, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PANK2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with phenylalanine at codon 19 of the PANK2 protein (p.Leu19Phe). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and phenylalanine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Benign
N
MutationTaster
Benign
D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of MoRF binding (P = 0.1472);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at