5-168568786-T-C

Variant names:

• chr5-168568786-T-C
• NM_024594.4:c.241A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024594.4(PANK3):​c.241A>G​(p.Asn81Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PANK3 NM_024594.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.25
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.787

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.241A>G	p.Asn81Asp	missense	Exon 2 of 7	NP_078870.1	Q9H999

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANK3	ENST00000239231.7	TSL:1 MANE Select	c.241A>G	p.Asn81Asp	missense	Exon 2 of 7	ENSP00000239231.6	Q9H999
	PANK3	ENST00000908768.1		c.241A>G	p.Asn81Asp	missense	Exon 2 of 6	ENSP00000578827.1
	PANK3	ENST00000522176.1	TSL:5	c.196A>G	p.Asn66Asp	missense	Exon 3 of 4	ENSP00000428631.1	E5RHA5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	D
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.3
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.5	D
REVEL	Pathogenic	0.68
Sift	Benign	0.15	T
Sift4G	Benign	0.52	T
Polyphen		0.58	P
Vest4		0.63
MutPred		0.70		Loss of MoRF binding (P = 0.0755)
MVP		0.96
MPC		1.4
ClinPred		0.96	D
GERP RS		4.6
Varity_R		0.78
gMVP		0.80
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

hg19: chr5-167995791;