rs158900

Variant names:

• chr5-168564949-A-G
• rs158900
• NM_024594.4:c.636-884T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024594.4(PANK3):​c.636-884T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,058 control chromosomes in the GnomAD database, including 8,978 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (8978 hom., cov: 32)
• Consequence: PANK3 NM_024594.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531

Genes affected

PANK3 (HGNC:19365): (pantothenate kinase 3) This gene encodes a protein belonging to the pantothenate kinase family. 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 CoA. This family member is expressed most abundantly in the liver. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANK3	NM_024594.4	c.636-884T>C		intron_variant	Intron 3 of 6	ENST00000239231.7	NP_078870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANK3	ENST00000239231.7	c.636-884T>C		intron_variant	Intron 3 of 6	1	NM_024594.4	ENSP00000239231.6
PANK3	ENST00000520504.1	n.52+1064T>C		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51781 AN: 151942 Hom.: 8967 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.361

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.341 AC: 51812 AN: 152058 Hom.: 8978 Cov.: 32 AF XY: 0.337 AC XY: 25021 AN XY: 74338

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.357

Alfa AF: 0.355 Hom.: 4447

Bravo AF: 0.328

Asia WGS AF: 0.297 AC: 1032 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.2
DANN	Benign	0.83

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: rs158900; hg19: chr5-167991954; COSMIC: COSV53322349; COSMIC: COSV53322349;