20-3889131-G-C

Variant names:

• chr20-3889131-G-C
• rs886044063
• ENST00000316562.9:c.31G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153638.4(PANK2):​c.31G>C​(p.Val11Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PANK2 NM_153638.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14726382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANK2	NM_153638.4	c.31G>C	p.Val11Leu	missense_variant	Exon 1 of 7		NP_705902.2
PANK2	NM_001324192.1	c.31G>C	p.Val11Leu	missense_variant	Exon 1 of 2		NP_001311121.1
PANK2	NM_024960.6	c.-246+227G>C		intron_variant	Intron 1 of 6		NP_079236.3
PANK2-AS1	XR_001754478.3	n.43C>G		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANK2	ENST00000316562.9	c.31G>C	p.Val11Leu	missense_variant	Exon 1 of 7	1		ENSP00000313377.4
PANK2	ENST00000497424.5	c.-246+227G>C		intron_variant	Intron 1 of 6	2		ENSP00000417609.1
PANK2	ENST00000495692.5	c.-538+115G>C		intron_variant	Intron 1 of 5	3		ENSP00000476745.1
PANK2-AS1	ENST00000702266.1	n.43C>G		non_coding_transcript_exon_variant	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	14
DANN	Benign	0.85
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.98
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.47	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	-0.029	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.25
Sift	Benign	0.20	T
Sift4G	Benign	0.64	T
Polyphen		0.17	B
Vest4		0.20
MutPred		0.32		Gain of catalytic residue at V11 (P = 0.0074);
MVP		0.79
MPC		0.44
ClinPred		0.15	T
GERP RS		2.9
Varity_R		0.055
gMVP		0.025

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

LitVar

Other links and lift over

dbSNP: rs886044063; hg19: chr20-3869778;