Variant 1-2509035-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_018216.4(PANK4):c.2134C>G(p.Leu712Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000345 in 1,448,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

PANK4
NM_018216.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.40

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23591909).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PANK4	NM_018216.4 linkuse as main transcript	c.2134C>G	p.Leu712Val	missense_variant	19/19	ENST00000378466.9	NP_060686.3	Q9NVE7
PANK4	XM_047424306.1 linkuse as main transcript	c.1693C>G	p.Leu565Val	missense_variant	19/19		XP_047280262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PANK4	ENST00000378466.9 linkuse as main transcript	c.2134C>G	p.Leu712Val	missense_variant	19/19	1	NM_018216.4	ENSP00000367727.5	Q9NVE7
PANK4	ENST00000435556.8 linkuse as main transcript	c.2017C>G	p.Leu673Val	missense_variant	19/19	2		ENSP00000421433.3	E9PHT6
PANK4	ENST00000505228.5 linkuse as main transcript	n.*252C>G		non_coding_transcript_exon_variant	16/16	5		ENSP00000425932.1	H0YA26
PANK4	ENST00000505228.5 linkuse as main transcript	n.*252C>G		3_prime_UTR_variant	16/16	5		ENSP00000425932.1	H0YA26

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000427

AC:

AN:

234012

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128256

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000345

AC:

AN:

1448954

Hom.:

Cov.:

AF XY:

0.00000555

AC XY:

AN XY:

721090

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2024

The c.2134C>G (p.L712V) alteration is located in exon 19 (coding exon 19) of the PANK4 gene. This alteration results from a C to G substitution at nucleotide position 2134, causing the leucine (L) at amino acid position 712 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.75

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.031

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.88

D;.

M_CAP

Benign

0.030

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.6

D;.

REVEL

Benign

0.093

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.60

T;T

Vest4

0.23

MVP

0.10

MPC

0.63

ClinPred

0.13

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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