rs3824603

Positions:

• chr10-89583850-G-A

Variant summary

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

The NM_148977.3(PANK1):​c.*556C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,376 control chromosomes in the GnomAD database, including 4,924 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 0.24 (4908 hom., cov: 32)
  • Exomes 𝑓: 0.28 (16 hom.)
• Consequence: PANK1 NM_148977.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.271

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PANK1	NM_148977.3	c.*556C>T		3_prime_UTR_variant	7/7	ENST00000307534.10	NP_683878.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PANK1	ENST00000307534.10	c.*556C>T		3_prime_UTR_variant	7/7	1	NM_148977.3	ENSP00000302108
PANK1	ENST00000322191.10	c.*556C>T		3_prime_UTR_variant	6/6	1		ENSP00000318526
PANK1	ENST00000342512.4	c.*556C>T		3_prime_UTR_variant	7/7	1		ENSP00000345118	P1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36891 AN: 151844 Hom.: 4900 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.235

GnomAD4 exome AF: 0.280 AC: 116 AN: 414 Hom.: 16 Cov.: 0 AF XY: 0.288 AC XY: 72 AN XY: 250

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.375

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.252

Gnomad4 NFE exome AF: 0.321

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.243 AC: 36904 AN: 151962 Hom.: 4908 Cov.: 32 AF XY: 0.247 AC XY: 18361 AN XY: 74258

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.232

Alfa AF: 0.265 Hom.: 2261

Bravo AF: 0.238

Asia WGS AF: 0.368 AC: 1281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.60

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: rs3824603; hg19: chr10-91343607; COSMIC: COSV56811648;