1-2510767-A-C

Position:

• chr1-2510767-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018216.4(PANK4):​c.1849T>G​(p.Cys617Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PANK4 NM_018216.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.50

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PANK4	NM_018216.4	c.1849T>G	p.Cys617Gly	missense_variant	16/19	ENST00000378466.9	NP_060686.3
PANK4	XM_047424306.1	c.1408T>G	p.Cys470Gly	missense_variant	16/19		XP_047280262.1
PANK4	XR_241034.4	n.1843-19T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PANK4	ENST00000378466.9	c.1849T>G	p.Cys617Gly	missense_variant	16/19	1	NM_018216.4	ENSP00000367727.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 28, 2022

The c.1849T>G (p.C617G) alteration is located in exon 16 (coding exon 16) of the PANK4 gene. This alteration results from a T to G substitution at nucleotide position 1849, causing the cysteine (C) at amino acid position 617 to be replaced by a glycine (G). 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	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	31
DANN	Benign	0.97
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D;.
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.70	T
REVEL	Uncertain	0.41
Sift4G	Benign	0.12	T;T
Vest4		0.90
MVP		0.45
MPC		1.7
ClinPred		0.99	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-2442206;