rs1013737590

Variant names:

• chr10-89611948-C-A
• rs1013737590
• NM_148977.3:c.393G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_148977.3(PANK1):​c.393G>T​(p.Glu131Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PANK1 NM_148977.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.10
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38060275).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANK1	NM_148977.3	MANE Select	c.393G>T	p.Glu131Asp	missense	Exon 2 of 7	NP_683878.2	A0A8C8KBT8
	PANK1	NM_148978.3		c.129G>T	p.Glu43Asp	missense	Exon 2 of 7	NP_683879.1	Q8TE04-2
	PANK1	NM_138316.4		c.129G>T	p.Glu43Asp	missense	Exon 2 of 6	NP_612189.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANK1	ENST00000307534.10	TSL:1 MANE Select	c.393G>T	p.Glu131Asp	missense	Exon 2 of 7	ENSP00000302108.5	A0A8C8KBT8
	PANK1	ENST00000342512.4	TSL:1	c.129G>T	p.Glu43Asp	missense	Exon 2 of 7	ENSP00000345118.3	Q8TE04-2
	PANK1	ENST00000322191.10	TSL:1	c.129G>T	p.Glu43Asp	missense	Exon 2 of 6	ENSP00000318526.6	Q8TE04-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461856 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111986

Other (OTH) AF: 0.0000662 AC: 4 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.73	D
Eigen	Benign	-0.11
Eigen_PC	Benign	0.038
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.38	T
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Benign	1.4	L
PhyloP100		1.1
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.56
Sift	Benign	0.073	T
Sift4G	Benign	0.11	T
Polyphen		0.99	D
Vest4		0.60
MutPred		0.35		Loss of methylation at K271 (P = 0.075)
MVP		0.97
MPC		1.5
ClinPred		0.94	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.60
Mutation Taster		=66/34	polymorphism

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: rs1013737590; hg19: chr10-91371705;