rs137852967

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM5

The NM_001386393.1(PANK2):​c.1253C>A​(p.Thr418Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T418M) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PANK2
NM_001386393.1 missense

Scores

2
7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.14
Variant links:
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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr20-3918717-C-T is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PANK2NM_001386393.1 linkc.1253C>A p.Thr418Lys missense_variant Exon 6 of 7 ENST00000610179.7 NP_001373322.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PANK2ENST00000610179.7 linkc.1253C>A p.Thr418Lys missense_variant Exon 6 of 7 1 NM_001386393.1 ENSP00000477429.2 Q9BZ23-4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461872
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Uncertain
25
DANN
Benign
0.85
DEOGEN2
Uncertain
0.70
.;.;D;.;.
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.043
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.60
.;T;T;T;T
M_CAP
Uncertain
0.18
D
MetaRNN
Uncertain
0.45
T;T;T;T;T
MetaSVM
Uncertain
0.65
D
MutationAssessor
Benign
0.94
.;.;L;.;.
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-1.6
N;.;N;.;.
REVEL
Uncertain
0.62
Sift
Benign
0.91
T;.;T;.;.
Sift4G
Benign
0.87
T;T;T;T;T
Polyphen
0.32
.;.;B;.;.
Vest4
0.74
MutPred
0.46
.;.;Gain of MoRF binding (P = 0.0168);.;.;
MVP
0.96
MPC
0.60
ClinPred
0.47
T
GERP RS
3.2
Varity_R
0.54
gMVP
0.84

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-3899364; API