rs158900

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.353 AC: 14625 AN: 41456

American (AMR) AF: 0.265 AC: 4052 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1474 AN: 3468

East Asian (EAS) AF: 0.151 AC: 780 AN: 5180

South Asian (SAS) AF: 0.456 AC: 2199 AN: 4820

European-Finnish (FIN) AF: 0.347 AC: 3665 AN: 10554

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23862 AN: 67986

Other (OTH) AF: 0.357 AC: 755 AN: 2112

Alfa AF: 0.351 Hom.: 5958

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
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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