Genetic Variant PANK1:c.-81G>A (chr10-89644972-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_148977.3(PANK1):c.-81G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00448 in 1,575,870 control chromosomes in the GnomAD database, including 293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 151 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 142 hom. )

Consequence

PANK1
NM_148977.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.539

Publications

3 publications found

Variant links:

Genes affected

PANK1 (HGNC:8598): (pantothenate kinase 1) This gene encodes a member of the pantothenate kinase family. Pantothenate kinases are key regulatory enzymes in the biosynthesis of coenzyme A (CoA). The encoded protein catalyzes the first and rate-limiting enzymatic reaction in CoA biosynthesis and is regulated by CoA through feedback inhibition. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. This gene and an intronic miRNA on the same strand are co-regulated by the tumor suppressor p53 (see PMID 20833636). [provided by RefSeq, Apr 2011]

PANK1 links:

ENSG00000235100 (HGNC:):

ENSG00000235100 links:

PANK1-AS1 (HGNC:55718): (PANK1 antisense RNA 1)

PANK1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013233721).

BP6

Variant 10-89644972-C-T is Benign according to our data. Variant chr10-89644972-C-T is described in ClinVar as Benign. ClinVar VariationId is 768376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0826 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148977.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PANK1	NM_148977.3	MANE Select	c.-81G>A	5_prime_UTR	Exon 1 of 7	NP_683878.2	A0A8C8KBT8
PANK1-AS1	NR_184342.1		n.86+773C>T	intron	N/A
PANK1-AS1	NR_184343.1		n.86+773C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PANK1	ENST00000307534.10	TSL:1 MANE Select	c.-81G>A	5_prime_UTR	Exon 1 of 7	ENSP00000302108.5	A0A8C8KBT8
PANK1	ENST00000874690.1		c.-81G>A	5_prime_UTR	Exon 1 of 6	ENSP00000544749.1
ENSG00000235100	ENST00000777460.1		n.461-9907G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0242

AC:

3672

AN:

152008

Hom.:

149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0849

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00675

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.0196

GnomAD2 exomes

AF:

0.00460

AC:

926

AN:

201434

AF XY:

0.00352

show subpopulations

Gnomad AFR exome

AF:

0.0847

Gnomad AMR exome

AF:

0.00368

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000157

Gnomad OTH exome

AF:

0.00302

GnomAD4 exome

AF:

0.00237

AC:

3380

AN:

1423754

Hom.:

142

Cov.:

AF XY:

0.00203

AC XY:

1435

AN XY:

707680

show subpopulations

African (AFR)

AF:

0.0942

AC:

2787

AN:

29574

American (AMR)

AF:

0.00427

AC:

173

AN:

40552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25032

East Asian (EAS)

AF:

0.00

AC:

AN:

34576

South Asian (SAS)

AF:

0.000303

AC:

AN:

82432

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51510

Middle Eastern (MID)

AF:

0.00337

AC:

AN:

5038

European-Non Finnish (NFE)

AF:

0.0000629

AC:

AN:

1096310

Other (OTH)

AF:

0.00526

AC:

309

AN:

58730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

189

378

567

756

945

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<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:

0.0242

AC:

3684

AN:

152116

Hom.:

151

Cov.:

AF XY:

0.0238

AC XY:

1774

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0849

AC:

3525

AN:

41512

American (AMR)

AF:

0.00674

AC:

103

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000177

AC:

AN:

67956

Other (OTH)

AF:

0.0194

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

178

355

533

710

888

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.00350

Hom.:

Bravo

AF:

0.0278

ESP6500AA

AF:

0.0671

AC:

268

ESP6500EA

AF:

0.000238

AC:

ExAC

AF:

0.00678

AC:

807

Asia WGS

AF:

0.00409

AC:

AN:

3436

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.17

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0013

MetaSVM

Uncertain

-0.22

MutationAssessor

Benign

0.55

PhyloP100

0.54

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.22

REVEL

Benign

0.23

Sift

Benign

0.29

Sift4G

Benign

0.20

Polyphen

0.0010

Vest4

0.095

MutPred

0.23

Gain of solvent accessibility (P = 0.0097)

MVP

0.80

MPC

0.72

ClinPred

0.0075

GERP RS

1.1

PromoterAI

-0.091

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.063

gMVP

0.095

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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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