10-89592893-C-T

Position:

• chr10-89592893-C-T

Variant summary

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

The NM_148977.3(PANK1):​c.1200+304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0848 in 533,592 control chromosomes in the GnomAD database, including 2,246 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 0.074 (548 hom., cov: 32)
  • Exomes 𝑓: 0.089 (1698 hom.)
• Consequence: PANK1 NM_148977.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421

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=-0.51).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PANK1	NM_148977.3	c.1200+304G>A		intron_variant		ENST00000307534.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PANK1	ENST00000307534.10	c.1200+304G>A		intron_variant		1	NM_148977.3
PANK1	ENST00000322191.10	c.759+304G>A		intron_variant		1
PANK1	ENST00000342512.4	c.936+304G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0742 AC: 11297 AN: 152198 Hom.: 541 Cov.: 32

Gnomad AFR AF: 0.0200

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.0752

Gnomad FIN AF: 0.0678

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0693

GnomAD4 exome AF: 0.0890 AC: 33921 AN: 381276 Hom.: 1698 AF XY: 0.0895 AC XY: 18798 AN XY: 210088

Gnomad4 AFR exome AF: 0.0193

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.0709

Gnomad4 EAS exome AF: 0.0149

Gnomad4 SAS exome AF: 0.0879

Gnomad4 FIN exome AF: 0.0665

Gnomad4 NFE exome AF: 0.0992

Gnomad4 OTH exome AF: 0.0825

GnomAD4 genome AF: 0.0742 AC: 11306 AN: 152316 Hom.: 548 Cov.: 32 AF XY: 0.0732 AC XY: 5454 AN XY: 74466

Gnomad4 AFR AF: 0.0200

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0755

Gnomad4 EAS AF: 0.0212

Gnomad4 SAS AF: 0.0750

Gnomad4 FIN AF: 0.0678

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0686

Alfa AF: 0.0911 Hom.: 113

Bravo AF: 0.0741

Asia WGS AF: 0.0520 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17481096; hg19: chr10-91352650;