rs2296616

Positions:

• chr10-89593209-G-A
• chr10-89593209-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_148977.3(PANK1):​c.1188C>T​(p.Cys396=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,612,514 control chromosomes in the GnomAD database, including 273,740 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 0.61 (29070 hom., cov: 32)
  • Exomes 𝑓: 0.57 (244670 hom.)
• Consequence: PANK1 NM_148977.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20

Genes affected

PANK1 (HGNC:8598): (pantothenate kinase 1) This gene encodes a member of the pantothenate kinase family. Pantothenate kinases are key regulatory enzymes in the biosynthesis of coenzyme A (CoA). The encoded protein catalyzes the first and rate-limiting enzymatic reaction in CoA biosynthesis and is regulated by CoA through feedback inhibition. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. This gene and an intronic miRNA on the same strand are co-regulated by the tumor suppressor p53 (see PMID 20833636). [provided by RefSeq, Apr 2011]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=2.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PANK1	NM_148977.3	c.1188C>T	p.Cys396=	synonymous_variant	5/7	ENST00000307534.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PANK1	ENST00000307534.10	c.1188C>T	p.Cys396=	synonymous_variant	5/7	1	NM_148977.3
PANK1	ENST00000342512.4	c.924C>T	p.Cys308=	synonymous_variant	5/7	1		P1
PANK1	ENST00000322191.10	c.747C>T	p.Cys249=	synonymous_variant	4/6	1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93047 AN: 151910 Hom.: 29025 Cov.: 32

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.590

GnomAD3 exomes AF: 0.619 AC: 155234 AN: 250692 Hom.: 49636 AF XY: 0.610 AC XY: 82595 AN XY: 135440

Gnomad AFR exome AF: 0.700

Gnomad AMR exome AF: 0.706

Gnomad ASJ exome AF: 0.554

Gnomad EAS exome AF: 0.936

Gnomad SAS exome AF: 0.635

Gnomad FIN exome AF: 0.562

Gnomad NFE exome AF: 0.544

Gnomad OTH exome AF: 0.591

GnomAD4 exome AF: 0.574 AC: 837606 AN: 1460486 Hom.: 244670 Cov.: 39 AF XY: 0.574 AC XY: 416736 AN XY: 726644

Gnomad4 AFR exome AF: 0.706

Gnomad4 AMR exome AF: 0.694

Gnomad4 ASJ exome AF: 0.548

Gnomad4 EAS exome AF: 0.926

Gnomad4 SAS exome AF: 0.635

Gnomad4 FIN exome AF: 0.558

Gnomad4 NFE exome AF: 0.548

Gnomad4 OTH exome AF: 0.588

GnomAD4 genome AF: 0.613 AC: 93146 AN: 152028 Hom.: 29070 Cov.: 32 AF XY: 0.619 AC XY: 45978 AN XY: 74306

Gnomad4 AFR AF: 0.695

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.933

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.592

Alfa AF: 0.562 Hom.: 32369

Bravo AF: 0.624

Asia WGS AF: 0.789 AC: 2743 AN: 3478

EpiCase AF: 0.547

EpiControl AF: 0.535

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.90

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: rs2296616; hg19: chr10-91352966;