rs1075374

Positions:

• chr10-89617218-C-A
• chr10-89617218-C-G
• chr10-89617218-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.293-5170G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,204 control chromosomes in the GnomAD database, including 2,205 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 0.15 (2205 hom., cov: 33)
• Consequence: PANK1 NM_148977.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PANK1	NM_148977.3	c.293-5170G>T		intron_variant		ENST00000307534.10	NP_683878.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PANK1	ENST00000307534.10	c.293-5170G>T		intron_variant		1	NM_148977.3	ENSP00000302108
PANK1	ENST00000322191.10	c.29-5170G>T		intron_variant		1		ENSP00000318526
PANK1	ENST00000342512.4	c.29-5170G>T		intron_variant		1		ENSP00000345118	P1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23095 AN: 152086 Hom.: 2208 Cov.: 33

Gnomad AFR AF: 0.0672

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.152 AC: 23095 AN: 152204 Hom.: 2205 Cov.: 33 AF XY: 0.158 AC XY: 11790 AN XY: 74408

Gnomad4 AFR AF: 0.0674

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.150

Alfa AF: 0.148 Hom.: 878

Bravo AF: 0.143

Asia WGS AF: 0.333 AC: 1155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.66

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: rs1075374; hg19: chr10-91376975;