10-89588762-C-T

Variant names:

• chr10-89588762-C-T
• rs1210160980
• NM_148977.3:c.1216G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_148977.3(PANK1):​c.1216G>A​(p.Val406Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PANK1 NM_148977.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.15
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1216G>A	p.Val406Met	missense	Exon 6 of 7	NP_683878.2	A0A8C8KBT8
	PANK1	NM_148978.3		c.952G>A	p.Val318Met	missense	Exon 6 of 7	NP_683879.1	Q8TE04-2
	PANK1	NM_138316.4		c.775G>A	p.Val259Met	missense	Exon 5 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.1216G>A	p.Val406Met	missense	Exon 6 of 7	ENSP00000302108.5	A0A8C8KBT8
	PANK1	ENST00000342512.4	TSL:1	c.952G>A	p.Val318Met	missense	Exon 6 of 7	ENSP00000345118.3	Q8TE04-2
	PANK1	ENST00000322191.10	TSL:1	c.775G>A	p.Val259Met	missense	Exon 5 of 6	ENSP00000318526.6	Q8TE04-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000424 AC: 1 AN: 235588 AF XY: 0.00000785

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000912

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

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	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.95	D
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.45	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		6.1
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.8	D
REVEL	Pathogenic	0.86
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.75		Gain of sheet (P = 0.0827)
MVP		0.96
MPC		1.6
ClinPred		0.93	D
GERP RS		5.7
Varity_R		0.74
gMVP		0.88
Mutation Taster		=36/64	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1210160980; hg19: chr10-91348519;