20-3889112-C-T
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS1
The ENST00000316562.9(PANK2):c.12C>T(p.Leu4=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000672 in 1,547,492 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L4L) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000061 ( 1 hom. )
Consequence
PANK2
ENST00000316562.9 synonymous
ENST00000316562.9 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.207
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 Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
Variant 20-3889112-C-T is Benign according to our data. Variant chr20-3889112-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 286784.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-0.207 with no splicing effect.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000609 (85/1395296) while in subpopulation MID AF= 0.0048 (23/4796). AF 95% confidence interval is 0.00328. There are 1 homozygotes in gnomad4_exome. There are 46 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PANK2-AS1 | XR_001754478.3 | n.62G>A | non_coding_transcript_exon_variant | 1/2 | ||||
| PANK2 | NM_153638.4 | c.12C>T | p.Leu4= | synonymous_variant | 1/7 | NP_705902.2 | ||
| PANK2 | NM_001324192.1 | c.12C>T | p.Leu4= | synonymous_variant | 1/2 | NP_001311121.1 | ||
| PANK2 | NM_024960.6 | c.-246+208C>T | intron_variant | NP_079236.3 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| PANK2 | ENST00000316562.9 | c.12C>T | p.Leu4= | synonymous_variant | 1/7 | 1 | ENSP00000313377 | A2 | ||
| PANK2-AS1 | ENST00000702266.1 | n.62G>A | non_coding_transcript_exon_variant | 1/1 | ||||||
| PANK2 | ENST00000495692.5 | c.-538+96C>T | intron_variant | 3 | ENSP00000476745 | |||||
| PANK2 | ENST00000497424.5 | c.-246+208C>T | intron_variant | 2 | ENSP00000417609 |
Frequencies
GnomAD3 genomes 0.000125 AC: 19AN: 152196Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000791 AC: 12AN: 151644Hom.: 0 AF XY: 0.0000621 AC XY: 5AN XY: 80530
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GnomAD4 exome AF: 0.0000609 AC: 85AN: 1395296Hom.: 1 Cov.: 31 AF XY: 0.0000669 AC XY: 46AN XY: 687954
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GnomAD4 genome 0.000125 AC: 19AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74352
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2023 | PANK2: BP4, BP7 - |
| Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 05, 2016 | - - |
Pigmentary pallidal degeneration Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 30, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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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