Genetic Variant PANK3:c.29-15_29-11delTTTTT (chr5-168569008-GAAAAA-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_024594.4(PANK3):c.29-15_29-11delTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00226 in 91,144 control chromosomes in the GnomAD database, including 5 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0049 ( 5 hom. )

Consequence

PANK3
NM_024594.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.764

Publications

0 publications found

Variant links:

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]

PANK3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 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.29-15_29-11delTTTTT		intron	N/A	NP_078870.1	Q9H999

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PANK3	ENST00000239231.7	TSL:1 MANE Select	c.29-15_29-11delTTTTT	intron	N/A	ENSP00000239231.6	Q9H999
PANK3	ENST00000908768.1		c.29-15_29-11delTTTTT	intron	N/A	ENSP00000578827.1
PANK3	ENST00000522176.1	TSL:5	c.-17-15_-17-11delTTTTT	intron	N/A	ENSP00000428631.1	E5RHA5

Frequencies

GnomAD3 genomes

AF:

0.0000797

AC:

AN:

50212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000349

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0248

AC:

129

AN:

5208

AF XY:

0.0224

show subpopulations

Gnomad AFR exome

AF:

0.0417

Gnomad AMR exome

AF:

0.0302

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0103

Gnomad FIN exome

AF:

0.0134

Gnomad NFE exome

AF:

0.0267

Gnomad OTH exome

AF:

0.0268

GnomAD4 exome

AF:

0.00494

AC:

202

AN:

40910

Hom.:

AF XY:

0.00562

AC XY:

121

AN XY:

21542

show subpopulations

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

African (AFR)

AF:

0.00743

AC:

AN:

808

American (AMR)

AF:

0.0112

AC:

AN:

1512

Ashkenazi Jewish (ASJ)

AF:

0.00188

AC:

AN:

1064

East Asian (EAS)

AF:

0.000728

AC:

AN:

4120

South Asian (SAS)

AF:

0.0121

AC:

AN:

910

European-Finnish (FIN)

AF:

0.00554

AC:

AN:

3070

Middle Eastern (MID)

AF:

0.00420

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00506

AC:

137

AN:

27090

Other (OTH)

AF:

0.00381

AC:

AN:

2098

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.385

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000796

AC:

AN:

50234

Hom.:

Cov.:

AF XY:

0.0000928

AC XY:

AN XY:

21548

show subpopulations

African (AFR)

AF:

0.000223

AC:

AN:

13446

American (AMR)

AF:

0.00

AC:

AN:

2988

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1528

East Asian (EAS)

AF:

0.00

AC:

AN:

948

South Asian (SAS)

AF:

0.00

AC:

AN:

904

European-Finnish (FIN)

AF:

0.00

AC:

AN:

662

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0000349

AC:

AN:

28674

Other (OTH)

AF:

0.00

AC:

AN:

560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.76

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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5-168569008-GAAAAAAAAAAAAAAAA-GAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over