Genetic Variant PANK3:c.29-11dupT (chr5-168569008-G-GA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_024594.4(PANK3):c.29-11dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 1188 hom., cov: 0)

Exomes 𝑓: 0.026 ( 0 hom. )

Consequence

PANK3
NM_024594.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 5-168569008-G-GA is Benign according to our data. Variant chr5-168569008-G-GA is described in ClinVar as Benign. ClinVar VariationId is 2776131.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

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.29-11dupT		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_29-10insT	intron	N/A	ENSP00000239231.6	Q9H999
PANK3	ENST00000908768.1		c.29-11_29-10insT	intron	N/A	ENSP00000578827.1
PANK3	ENST00000522176.1	TSL:5	c.-17-11_-17-10insT	intron	N/A	ENSP00000428631.1	E5RHA5

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

8313

AN:

50082

Hom.:

1190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0794

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.0405

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.0796

Gnomad MID

AF:

0.106

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.185

GnomAD2 exomes

AF:

0.00307

AC:

AN:

5208

AF XY:

0.00190

show subpopulations

Gnomad AFR exome

AF:

0.00833

Gnomad AMR exome

AF:

0.00275

Gnomad ASJ exome

AF:

0.0204

Gnomad EAS exome

AF:

0.00256

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00253

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0263

AC:

1075

AN:

40838

Hom.:

Cov.:

AF XY:

0.0277

AC XY:

595

AN XY:

21498

show subpopulations

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

African (AFR)

AF:

0.00995

AC:

AN:

804

American (AMR)

AF:

0.00594

AC:

AN:

1514

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

AN:

1064

East Asian (EAS)

AF:

0.00243

AC:

AN:

4116

South Asian (SAS)

AF:

0.0233

AC:

AN:

902

European-Finnish (FIN)

AF:

0.00618

AC:

AN:

3074

Middle Eastern (MID)

AF:

0.0248

AC:

AN:

242

European-Non Finnish (NFE)

AF:

0.0348

AC:

939

AN:

27016

Other (OTH)

AF:

0.0190

AC:

AN:

2106

⚠️ 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: 0.377

Heterozygous variant carriers

151

227

302

378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

112

140

<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:

0.166

AC:

8310

AN:

50104

Hom.:

1188

Cov.:

AF XY:

0.159

AC XY:

3410

AN XY:

21486

show subpopulations

African (AFR)

AF:

0.0794

AC:

1066

AN:

13424

American (AMR)

AF:

0.118

AC:

351

AN:

2978

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

329

AN:

1530

East Asian (EAS)

AF:

0.0406

AC:

AN:

936

South Asian (SAS)

AF:

0.236

AC:

215

AN:

910

European-Finnish (FIN)

AF:

0.0796

AC:

AN:

666

Middle Eastern (MID)

AF:

0.109

AC:

AN:

European-Non Finnish (NFE)

AF:

0.212

AC:

6053

AN:

28584

Other (OTH)

AF:

0.185

AC:

103

AN:

558

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

251

502

754

1005

1256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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