Genetic Variant PANK3:c.29-12_29-11dupTT (chr5-168569008-G-GAA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_024594.4(PANK3):c.29-12_29-11dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0094 ( 16 hom., cov: 0)

Exomes 𝑓: 0.0029 ( 0 hom. )

Consequence

PANK3
NM_024594.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.35

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: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00936 (469/50116) while in subpopulation SAS AF = 0.0356 (32/900). AF 95% confidence interval is 0.0259. There are 16 homozygotes in GnomAd4. There are 209 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 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_29-11dupTT		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.29-11_29-10insTT	intron	N/A	ENSP00000239231.6	Q9H999
PANK3	ENST00000908768.1		c.29-11_29-10insTT	intron	N/A	ENSP00000578827.1
PANK3	ENST00000522176.1	TSL:5	c.-17-11_-17-10insTT	intron	N/A	ENSP00000428631.1	E5RHA5

Frequencies

GnomAD3 genomes

AF:

0.00936

AC:

469

AN:

50094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.0109

Gnomad AMR

AF:

0.00737

Gnomad ASJ

AF:

0.000657

Gnomad EAS

AF:

0.00211

Gnomad SAS

AF:

0.0355

Gnomad FIN

AF:

0.00758

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00672

Gnomad OTH

AF:

0.00536

GnomAD4 exome

AF:

0.00286

AC:

117

AN:

40938

Hom.:

Cov.:

AF XY:

0.00329

AC XY:

AN XY:

21560

show subpopulations

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

African (AFR)

AF:

0.00124

AC:

AN:

808

American (AMR)

AF:

0.00395

AC:

AN:

1520

Ashkenazi Jewish (ASJ)

AF:

0.00282

AC:

AN:

1062

East Asian (EAS)

AF:

0.00121

AC:

AN:

4120

South Asian (SAS)

AF:

0.00110

AC:

AN:

912

European-Finnish (FIN)

AF:

0.00130

AC:

AN:

3080

Middle Eastern (MID)

AF:

0.00413

AC:

AN:

242

European-Non Finnish (NFE)

AF:

0.00347

AC:

AN:

27092

Other (OTH)

AF:

0.000951

AC:

AN:

2102

⚠️ 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: 0.301

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00936

AC:

469

AN:

50116

Hom.:

Cov.:

AF XY:

0.00972

AC XY:

209

AN XY:

21506

show subpopulations

African (AFR)

AF:

0.0154

AC:

207

AN:

13426

American (AMR)

AF:

0.00736

AC:

AN:

2988

Ashkenazi Jewish (ASJ)

AF:

0.000657

AC:

AN:

1522

East Asian (EAS)

AF:

0.00211

AC:

AN:

948

South Asian (SAS)

AF:

0.0356

AC:

AN:

900

European-Finnish (FIN)

AF:

0.00758

AC:

AN:

660

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00672

AC:

192

AN:

28590

Other (OTH)

AF:

0.00536

AC:

AN:

560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.4

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-GAAAAAAAAAAAAAAAAAA

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