rs12073504

Positions:

• chr1-2521540-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000378466.9(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 ENST00000378466.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1925 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PANK4	NM_018216.4	c.207+178G>C		intron_variant		ENST00000378466.9	NP_060686.3
PANK4	XM_011541708.4	c.207+178G>C		intron_variant			XP_011540010.2
PANK4	XM_047424306.1	c.-235+178G>C		intron_variant			XP_047280262.1
PANK4	XR_241034.4	n.216+178G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PANK4	ENST00000378466.9	c.207+178G>C		intron_variant		1	NM_018216.4	ENSP00000367727	P1

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1921 AN: 152200 Hom.: 28 Cov.: 33

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.: 72 Cov.: 6 AF XY: 0.0111 AC XY: 3368 AN XY: 303886

Gnomad4 AFR exome AF: 0.0248

Gnomad4 AMR exome AF: 0.00206

Gnomad4 ASJ exome AF: 0.00193

Gnomad4 EAS exome AF: 0.0157

Gnomad4 SAS exome AF: 0.0355

Gnomad4 FIN exome AF: 0.00513

Gnomad4 NFE exome AF: 0.00585

Gnomad4 OTH exome AF: 0.00820

GnomAD4 genome AF: 0.0126 AC: 1925 AN: 152318 Hom.: 28 Cov.: 33 AF XY: 0.0125 AC XY: 932 AN XY: 74486

Gnomad4 AFR AF: 0.0259

Gnomad4 AMR AF: 0.00379

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.0251

Gnomad4 SAS AF: 0.0354

Gnomad4 FIN AF: 0.00565

Gnomad4 NFE AF: 0.00606

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00752 Hom.: 3

Bravo AF: 0.0129

Asia WGS AF: 0.0310 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
DANN	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs12073504; hg19: chr1-2452979;