rs10509577

chr10-89592910-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_148977.3(PANK1):c.1200+287T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0477 in 526,544 control chromosomes in the GnomAD database, including 850 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 0.044 (229 hom., cov: 32)
  • Exomes 𝑓: 0.049 (621 hom.)
• Consequence: PANK1 NM_148977.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PANK1	NM_148977.3	c.1200+287T>C		intron_variant		ENST00000307534.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PANK1	ENST00000307534.10	c.1200+287T>C		intron_variant		1	NM_148977.3
PANK1	ENST00000322191.10	c.759+287T>C		intron_variant		1
PANK1	ENST00000342512.4	c.936+287T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0442 AC: 6723 AN: 152220 Hom.: 229 Cov.: 32

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0323

Gnomad ASJ AF: 0.0257

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.0592

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0713

Gnomad OTH AF: 0.0382

GnomAD4 exome AF: 0.0491 AC: 18388 AN: 374206 Hom.: 621 AF XY: 0.0464 AC XY: 9447 AN XY: 203764

Gnomad4 AFR exome AF: 0.0107

Gnomad4 AMR exome AF: 0.0211

Gnomad4 ASJ exome AF: 0.0235

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0137

Gnomad4 FIN exome AF: 0.0579

Gnomad4 NFE exome AF: 0.0695

Gnomad4 OTH exome AF: 0.0498

GnomAD4 genome AF: 0.0441 AC: 6721 AN: 152338 Hom.: 229 Cov.: 32 AF XY: 0.0418 AC XY: 3110 AN XY: 74486

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.0323

Gnomad4 ASJ AF: 0.0257

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00787

Gnomad4 FIN AF: 0.0592

Gnomad4 NFE AF: 0.0713

Gnomad4 OTH AF: 0.0378

Alfa AF: 0.0611 Hom.: 219

Bravo AF: 0.0410

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	0.13
Dann	Benign	0.73

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: rs10509577; hg19: chr10-91352667;