dbSNP rs12073504: PANK4:c.207+178G>C (chr1-2521540-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_018216.4(PANK4):c.207+178G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 719,502 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.013 ( 28 hom., cov: 33)

Exomes 𝑓: 0.0099 ( 72 hom. )

Consequence

PANK4
NM_018216.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0340

Publications

5 publications found

Variant links:

Genes affected

PANK4 (HGNC:19366): (pantothenate kinase 4 (inactive)) 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 most abundant in muscle but is expressed in all tissues. [provided by RefSeq, Jul 2008]

PANK4 Gene-Disease associations (from GenCC):

early-onset posterior polar cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
cataract
Inheritance: AD Classification: LIMITED Submitted by: G2P
cataract 49
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

PANK4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0126 (1925/152318) while in subpopulation SAS AF = 0.0354 (171/4828). AF 95% confidence interval is 0.0311. There are 28 homozygotes in GnomAd4. There are 932 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1925 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018216.4. 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
	PANK4	NM_018216.4	MANE Select	c.207+178G>C		intron	N/A	NP_060686.3	Q9NVE7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PANK4	ENST00000378466.9	TSL:1 MANE Select	c.207+178G>C	intron	N/A	ENSP00000367727.5	Q9NVE7
PANK4	ENST00000502770.2	TSL:1	n.*70G>C	non_coding_transcript_exon	Exon 2 of 3	ENSP00000425674.3	D6RJF3
PANK4	ENST00000502770.2	TSL:1	n.*70G>C	3_prime_UTR	Exon 2 of 3	ENSP00000425674.3	D6RJF3

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1921

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0250

Gnomad SAS

AF:

0.0352

Gnomad FIN

AF:

0.00565

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00606

Gnomad OTH

AF:

0.00527

GnomAD4 exome

AF:

0.00989

AC:

5610

AN:

567184

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

3368

AN XY:

303886

show subpopulations

African (AFR)

AF:

0.0248

AC:

399

AN:

16118

American (AMR)

AF:

0.00206

AC:

AN:

33940

Ashkenazi Jewish (ASJ)

AF:

0.00193

AC:

AN:

16616

East Asian (EAS)

AF:

0.0157

AC:

543

AN:

34556

South Asian (SAS)

AF:

0.0355

AC:

2091

AN:

58872

European-Finnish (FIN)

AF:

0.00513

AC:

184

AN:

35866

Middle Eastern (MID)

AF:

0.0192

AC:

AN:

3602

European-Non Finnish (NFE)

AF:

0.00585

AC:

1972

AN:

337136

Other (OTH)

AF:

0.00820

AC:

250

AN:

30478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

327

654

981

1308

1635

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.0126

AC:

1925

AN:

152318

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

932

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0259

AC:

1075

AN:

41572

American (AMR)

AF:

0.00379

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.0251

AC:

130

AN:

5184

South Asian (SAS)

AF:

0.0354

AC:

171

AN:

4828

European-Finnish (FIN)

AF:

0.00565

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00606

AC:

412

AN:

68012

Other (OTH)

AF:

0.00521

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

197

296

394

493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00752

Hom.:

Bravo

AF:

0.0129

Asia WGS

AF:

0.0310

AC:

106

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.0

(source)

DANN

Benign

0.52

PhyloP100

0.034

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(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

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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