chr5-168569008-GAA-G

Variant names:

• chr5-168569008-GAA-G
• rs368234880
• NM_024594.4:c.29-12_29-11delTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_024594.4(PANK3):​c.29-12_29-11delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 90,828 control chromosomes in the GnomAD database, including 56 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.012 (5 hom., cov: 0)
  • Exomes 𝑓: 0.027 (51 hom.)
• Consequence: PANK3 NM_024594.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.724
• Publications: 0 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0123 (615/50180) while in subpopulation AFR AF = 0.0403 (540/13404). AF 95% confidence interval is 0.0375. There are 5 homozygotes in GnomAd4. There are 268 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024594.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANK3	NM_024594.4	MANE Select	c.29-12_29-11delTT		intron	N/A	NP_078870.1	Q9H999

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANK3	ENST00000239231.7	TSL:1 MANE Select	c.29-12_29-11delTT		intron	N/A	ENSP00000239231.6	Q9H999
	PANK3	ENST00000908768.1		c.29-12_29-11delTT		intron	N/A	ENSP00000578827.1
	PANK3	ENST00000522176.1	TSL:5	c.-17-12_-17-11delTT		intron	N/A	ENSP00000428631.1	E5RHA5

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 614 AN: 50160 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00435

Gnomad ASJ AF: 0.00919

Gnomad EAS AF: 0.00105

Gnomad SAS AF: 0.00221

Gnomad FIN AF: 0.00152

Gnomad MID AF: 0.0303

Gnomad NFE AF: 0.00129

Gnomad OTH AF: 0.00893

GnomAD2 exomes AF: 0.0639 AC: 333 AN: 5208 AF XY: 0.0676

Gnomad AFR exome AF: 0.0271

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.0510

Gnomad EAS exome AF: 0.0769

Gnomad FIN exome AF: 0.0343

Gnomad NFE exome AF: 0.0672

Gnomad OTH exome AF: 0.0357

GnomAD4 exome AF: 0.0271 AC: 1102 AN: 40648 Hom.: 51 AF XY: 0.0275 AC XY: 588 AN XY: 21394

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0376 AC: 30 AN: 798

American (AMR) AF: 0.0372 AC: 56 AN: 1506

Ashkenazi Jewish (ASJ) AF: 0.0238 AC: 25 AN: 1052

East Asian (EAS) AF: 0.00873 AC: 36 AN: 4122

South Asian (SAS) AF: 0.0508 AC: 46 AN: 906

European-Finnish (FIN) AF: 0.0215 AC: 66 AN: 3066

Middle Eastern (MID) AF: 0.0207 AC: 5 AN: 242

European-Non Finnish (NFE) AF: 0.0292 AC: 784 AN: 26872

Other (OTH) AF: 0.0259 AC: 54 AN: 2084

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0123 AC: 615 AN: 50180 Hom.: 5 Cov.: 0 AF XY: 0.0125 AC XY: 268 AN XY: 21520

African (AFR) AF: 0.0403 AC: 540 AN: 13404

American (AMR) AF: 0.00435 AC: 13 AN: 2988

Ashkenazi Jewish (ASJ) AF: 0.00919 AC: 14 AN: 1524

East Asian (EAS) AF: 0.00105 AC: 1 AN: 948

South Asian (SAS) AF: 0.00221 AC: 2 AN: 904

European-Finnish (FIN) AF: 0.00152 AC: 1 AN: 660

Middle Eastern (MID) AF: 0.0313 AC: 2 AN: 64

European-Non Finnish (NFE) AF: 0.00129 AC: 37 AN: 28668

Other (OTH) AF: 0.00893 AC: 5 AN: 560

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.72
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: rs368234880; hg19: chr5-167996013;