10-89585939-C-T

Variant names:

• chr10-89585939-C-T
• rs719909
• NM_148977.3:c.1327-1474G>A

Variant summary

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

The NM_148977.3(PANK1):​c.1327-1474G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,152 control chromosomes in the GnomAD database, including 2,451 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 0.17 (2451 hom., cov: 32)
• Consequence: PANK1 NM_148977.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANK1	NM_148977.3	c.1327-1474G>A		intron_variant	Intron 6 of 6	ENST00000307534.10	NP_683878.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANK1	ENST00000307534.10	c.1327-1474G>A		intron_variant	Intron 6 of 6	1	NM_148977.3	ENSP00000302108.5
PANK1	ENST00000342512.4	c.1063-1474G>A		intron_variant	Intron 6 of 6	1		ENSP00000345118.3
PANK1	ENST00000322191.10	c.886-1474G>A		intron_variant	Intron 5 of 5	1		ENSP00000318526.6

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25626 AN: 152034 Hom.: 2447 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.163

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.169 AC: 25647 AN: 152152 Hom.: 2451 Cov.: 32 AF XY: 0.174 AC XY: 12956 AN XY: 74362

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.160

Alfa AF: 0.170 Hom.: 372

Bravo AF: 0.163

Asia WGS AF: 0.326 AC: 1132 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.49

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: rs719909; hg19: chr10-91345696;