rs727427

Variant names:

• chr10-89640627-T-C
• rs727427
• NM_148977.3:c.292+3973A>G

Variant summary

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

The NM_148977.3(PANK1):​c.292+3973A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,058 control chromosomes in the GnomAD database, including 9,388 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 0.33 (9388 hom., cov: 32)
• Consequence: PANK1 NM_148977.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 3 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]

ENSG00000235100 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANK1	NM_148977.3	c.292+3973A>G		intron_variant	Intron 1 of 6	ENST00000307534.10	NP_683878.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANK1	ENST00000307534.10	c.292+3973A>G		intron_variant	Intron 1 of 6	1	NM_148977.3	ENSP00000302108.5

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50679 AN: 151940 Hom.: 9352 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.334 AC: 50760 AN: 152058 Hom.: 9388 Cov.: 32 AF XY: 0.337 AC XY: 25018 AN XY: 74314

African (AFR) AF: 0.487 AC: 20180 AN: 41456

American (AMR) AF: 0.283 AC: 4317 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1101 AN: 3472

East Asian (EAS) AF: 0.299 AC: 1550 AN: 5182

South Asian (SAS) AF: 0.467 AC: 2254 AN: 4824

European-Finnish (FIN) AF: 0.334 AC: 3518 AN: 10546

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 17003 AN: 67982

Other (OTH) AF: 0.293 AC: 619 AN: 2112

Alfa AF: 0.306 Hom.: 1011

Bravo AF: 0.329

Asia WGS AF: 0.415 AC: 1442 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	1.5
DANN	Benign	0.82
PhyloP100		-0.18
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: rs727427; hg19: chr10-91400384;