10-89603827-A-G

Variant names:

• chr10-89603827-A-G
• rs1409354
• NM_148977.3:c.646-4322T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_148977.3(PANK1):​c.646-4322T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,008 control chromosomes in the GnomAD database, including 29,029 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 0.61 (29029 hom., cov: 31)
• Consequence: PANK1 NM_148977.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148977.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANK1	NM_148977.3	MANE Select	c.646-4322T>C		intron	N/A	NP_683878.2
	PANK1	NM_148978.3		c.382-4322T>C		intron	N/A	NP_683879.1
	PANK1	NM_138316.4		c.382-4322T>C		intron	N/A	NP_612189.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANK1	ENST00000307534.10	TSL:1 MANE Select	c.646-4322T>C		intron	N/A	ENSP00000302108.5
	PANK1	ENST00000342512.4	TSL:1	c.382-4322T>C		intron	N/A	ENSP00000345118.3
	PANK1	ENST00000322191.10	TSL:1	c.382-4322T>C		intron	N/A	ENSP00000318526.6

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92967 AN: 151890 Hom.: 28987 Cov.: 31

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.612 AC: 93063 AN: 152008 Hom.: 29029 Cov.: 31 AF XY: 0.618 AC XY: 45922 AN XY: 74280

African (AFR) AF: 0.693 AC: 28716 AN: 41466

American (AMR) AF: 0.628 AC: 9591 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1925 AN: 3470

East Asian (EAS) AF: 0.942 AC: 4859 AN: 5160

South Asian (SAS) AF: 0.622 AC: 2995 AN: 4818

European-Finnish (FIN) AF: 0.576 AC: 6070 AN: 10534

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36990 AN: 67978

Other (OTH) AF: 0.593 AC: 1252 AN: 2112

Alfa AF: 0.463 Hom.: 1312

Bravo AF: 0.624

Asia WGS AF: 0.790 AC: 2747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.75
PhyloP100		0.033
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1409354; hg19: chr10-91363584;