rs10727

Positions:

• chr10-89634350-A-G
• chr10-89634350-A-T

Variant summary

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

The NM_148977.3(PANK1):​c.292+10250T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,144 control chromosomes in the GnomAD database, including 50,267 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 0.81 (50267 hom., cov: 31)
• Consequence: PANK1 NM_148977.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

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]

PANK1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PANK1	NM_148977.3	c.292+10250T>C		intron_variant		ENST00000307534.10	NP_683878.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PANK1	ENST00000307534.10	c.292+10250T>C		intron_variant		1	NM_148977.3	ENSP00000302108.5
PANK1	ENST00000342512.4	c.28+9347T>C		intron_variant		1		ENSP00000345118.3
PANK1	ENST00000322191.10	c.28+9347T>C		intron_variant		1		ENSP00000318526.6
PANK1	ENST00000488482.1	n.261-7718T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122838 AN: 152024 Hom.: 50201 Cov.: 31

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.808 AC: 122964 AN: 152144 Hom.: 50267 Cov.: 31 AF XY: 0.814 AC XY: 60579 AN XY: 74382

Gnomad4 AFR AF: 0.917

Gnomad4 AMR AF: 0.815

Gnomad4 ASJ AF: 0.746

Gnomad4 EAS AF: 0.924

Gnomad4 SAS AF: 0.934

Gnomad4 FIN AF: 0.804

Gnomad4 NFE AF: 0.731

Gnomad4 OTH AF: 0.783

Alfa AF: 0.779 Hom.: 7900

Bravo AF: 0.807

Asia WGS AF: 0.928 AC: 3226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.5
DANN	Benign	0.81

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: rs10727; hg19: chr10-91394107;