NM_148977.3:c.293-5170G>T

Variant names:

• chr10-89617218-C-A
• rs1075374
• NM_148977.3:c.293-5170G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 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.293-5170G>T		intron	N/A	NP_683878.2
	PANK1	NM_148978.3		c.29-5170G>T		intron	N/A	NP_683879.1
	PANK1	NM_138316.4		c.29-5170G>T		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.293-5170G>T		intron	N/A	ENSP00000302108.5
	PANK1	ENST00000342512.4	TSL:1	c.29-5170G>T		intron	N/A	ENSP00000345118.3
	PANK1	ENST00000322191.10	TSL:1	c.29-5170G>T		intron	N/A	ENSP00000318526.6

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

African (AFR) AF: 0.0674 AC: 2797 AN: 41526

American (AMR) AF: 0.158 AC: 2424 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 505 AN: 3470

East Asian (EAS) AF: 0.453 AC: 2347 AN: 5176

South Asian (SAS) AF: 0.231 AC: 1115 AN: 4830

European-Finnish (FIN) AF: 0.222 AC: 2350 AN: 10578

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.164 AC: 11146 AN: 68010

Other (OTH) AF: 0.150 AC: 318 AN: 2114

Alfa AF: 0.148 Hom.: 984

Bravo AF: 0.143

Asia WGS AF: 0.333 AC: 1155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.66
PhyloP100		-0.069
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: rs1075374; hg19: chr10-91376975;