Variant 1-2512975-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018216.4(PANK4):c.1640C>T(p.Ala547Val) variant causes a missense change. The variant allele was found at a frequency of 0.344 in 1,611,998 control chromosomes in the GnomAD database, including 100,597 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A547S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.28 ( 7170 hom., cov: 35)

Exomes 𝑓: 0.35 ( 93427 hom. )

Consequence

PANK4
NM_018216.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.00

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009886503).

BP6

Variant 1-2512975-G-A is Benign according to our data. Variant chr1-2512975-G-A is described in ClinVar as [Benign]. Clinvar id is 2585653.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PANK4	NM_018216.4 linkuse as main transcript	c.1640C>T	p.Ala547Val	missense_variant	13/19	ENST00000378466.9
PANK4	XM_047424306.1 linkuse as main transcript	c.1199C>T	p.Ala400Val	missense_variant	13/19
PANK4	XR_241034.4 linkuse as main transcript	n.1649C>T		non_coding_transcript_exon_variant	13/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PANK4	ENST00000378466.9 linkuse as main transcript	c.1640C>T	p.Ala547Val	missense_variant	13/19	1	NM_018216.4	P1

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41906

AN:

152114

Hom.:

7171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0678

Gnomad AMI

AF:

0.507

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.377

Gnomad EAS

AF:

0.344

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.376

Gnomad OTH

AF:

0.315

GnomAD3 exomes

AF:

0.315

AC:

78659

AN:

249742

Hom.:

13382

AF XY:

0.322

AC XY:

43570

AN XY:

135392

show subpopulations

Gnomad AFR exome

AF:

0.0627

Gnomad AMR exome

AF:

0.232

Gnomad ASJ exome

AF:

0.375

Gnomad EAS exome

AF:

0.360

Gnomad SAS exome

AF:

0.241

Gnomad FIN exome

AF:

0.351

Gnomad NFE exome

AF:

0.375

Gnomad OTH exome

AF:

0.351

GnomAD4 exome

AF:

0.352

AC:

513284

AN:

1459764

Hom.:

93427

Cov.:

AF XY:

0.350

AC XY:

254196

AN XY:

726178

show subpopulations

Gnomad4 AFR exome

AF:

0.0539

Gnomad4 AMR exome

AF:

0.241

Gnomad4 ASJ exome

AF:

0.375

Gnomad4 EAS exome

AF:

0.380

Gnomad4 SAS exome

AF:

0.247

Gnomad4 FIN exome

AF:

0.353

Gnomad4 NFE exome

AF:

0.372

Gnomad4 OTH exome

AF:

0.335

GnomAD4 genome

AF:

0.275

AC:

41894

AN:

152234

Hom.:

7170

Cov.:

AF XY:

0.274

AC XY:

20419

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0676

Gnomad4 AMR

AF:

0.290

Gnomad4 ASJ

AF:

0.377

Gnomad4 EAS

AF:

0.344

Gnomad4 SAS

AF:

0.238

Gnomad4 FIN

AF:

0.346

Gnomad4 NFE

AF:

0.376

Gnomad4 OTH

AF:

0.312

Alfa

AF:

0.353

Hom.:

15473

Bravo

AF:

0.264

TwinsUK

AF:

0.357

AC:

1322

ALSPAC

AF:

0.368

AC:

1417

ESP6500AA

AF:

0.0717

AC:

316

ESP6500EA

AF:

0.375

AC:

3222

ExAC

AF:

0.312

AC:

37849

Asia WGS

AF:

0.219

AC:

761

AN:

3478

EpiCase

AF:

0.388

EpiControl

AF:

0.380

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cataract 49

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.66

T;.

MetaRNN

Benign

0.0099

T;T

MetaSVM

Benign

-0.87

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.31

REVEL

Benign

0.091

Sift4G

Benign

0.11

T;T

Vest4

0.050

MPC

0.66

ClinPred

0.028

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over