10-89588762-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANK1	NM_148977.3	c.1216G>A	p.Val406Met	missense_variant	Exon 6 of 7	ENST00000307534.10	NP_683878.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANK1	ENST00000307534.10	c.1216G>A	p.Val406Met	missense_variant	Exon 6 of 7	1	NM_148977.3	ENSP00000302108.5
PANK1	ENST00000342512.4	c.952G>A	p.Val318Met	missense_variant	Exon 6 of 7	1		ENSP00000345118.3
PANK1	ENST00000322191.10	c.775G>A	p.Val259Met	missense_variant	Exon 5 of 6	1		ENSP00000318526.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000424 AC: 1 AN: 235588 Hom.: 0 AF XY: 0.00000785 AC XY: 1 AN XY: 127372

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 SAS 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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1627G>A (p.V543M) alteration is located in exon 6 (coding exon 6) of the PANK1 gene. This alteration results from a G to A substitution at nucleotide position 1627, causing the valine (V) at amino acid position 543 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;D;D
M_CAP	Pathogenic	0.45	D
MetaRNN	Uncertain	0.62	D;D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.9	M;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Pathogenic	0.86
Sift	Uncertain	0.017	D;D;D
Sift4G	Uncertain	0.0080	D;T;T
Polyphen		1.0	D;B;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1210160980; hg19: chr10-91348519;