rs2296616

Variant names:

• chr10-89593209-G-A
• rs2296616
• NM_148977.3:c.1188C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-89593209-G-A
• chr10-89593209-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_148977.3(PANK1):​c.1188C>T​(p.Cys396Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,612,514 control chromosomes in the GnomAD database, including 273,740 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 0.61 (29070 hom., cov: 32)
  • Exomes 𝑓: 0.57 (244670 hom.)
• Consequence: PANK1 NM_148977.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 37 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=2.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANK1	NM_148977.3	c.1188C>T	p.Cys396Cys	synonymous_variant	Exon 5 of 7	ENST00000307534.10	NP_683878.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANK1	ENST00000307534.10	c.1188C>T	p.Cys396Cys	synonymous_variant	Exon 5 of 7	1	NM_148977.3	ENSP00000302108.5
PANK1	ENST00000342512.4	c.924C>T	p.Cys308Cys	synonymous_variant	Exon 5 of 7	1		ENSP00000345118.3
PANK1	ENST00000322191.10	c.747C>T	p.Cys249Cys	synonymous_variant	Exon 4 of 6	1		ENSP00000318526.6

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93047 AN: 151910 Hom.: 29025 Cov.: 32

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.590

GnomAD2 exomes AF: 0.619 AC: 155234 AN: 250692 AF XY: 0.610

Gnomad AFR exome AF: 0.700

Gnomad AMR exome AF: 0.706

Gnomad ASJ exome AF: 0.554

Gnomad EAS exome AF: 0.936

Gnomad FIN exome AF: 0.562

Gnomad NFE exome AF: 0.544

Gnomad OTH exome AF: 0.591

GnomAD4 exome AF: 0.574 AC: 837606 AN: 1460486 Hom.: 244670 Cov.: 39 AF XY: 0.574 AC XY: 416736 AN XY: 726644

African (AFR) AF: 0.706 AC: 23611 AN: 33436

American (AMR) AF: 0.694 AC: 31019 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 14317 AN: 26108

East Asian (EAS) AF: 0.926 AC: 36773 AN: 39692

South Asian (SAS) AF: 0.635 AC: 54775 AN: 86208

European-Finnish (FIN) AF: 0.558 AC: 29822 AN: 53408

Middle Eastern (MID) AF: 0.564 AC: 3247 AN: 5754

European-Non Finnish (NFE) AF: 0.548 AC: 608590 AN: 1110848

Other (OTH) AF: 0.588 AC: 35452 AN: 60330

GnomAD4 genome AF: 0.613 AC: 93146 AN: 152028 Hom.: 29070 Cov.: 32 AF XY: 0.619 AC XY: 45978 AN XY: 74306

African (AFR) AF: 0.695 AC: 28854 AN: 41494

American (AMR) AF: 0.628 AC: 9581 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1924 AN: 3470

East Asian (EAS) AF: 0.933 AC: 4818 AN: 5162

South Asian (SAS) AF: 0.627 AC: 3013 AN: 4808

European-Finnish (FIN) AF: 0.574 AC: 6067 AN: 10568

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36971 AN: 67950

Other (OTH) AF: 0.592 AC: 1251 AN: 2112

Alfa AF: 0.572 Hom.: 45628

Bravo AF: 0.624

Asia WGS AF: 0.789 AC: 2743 AN: 3478

EpiCase AF: 0.547

EpiControl AF: 0.535

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.90
PhyloP100		2.2
Mutation Taster		=89/11	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: rs2296616; hg19: chr10-91352966; COSMIC: COSV108144251; COSMIC: COSV108144251;