rs10509577

Variant names:

• chr10-89592910-A-G
• rs10509577
• NM_148977.3:c.1200+287T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_148977.3(PANK1):​c.1200+287T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0477 in 526,544 control chromosomes in the GnomAD database, including 850 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 0.044 (229 hom., cov: 32)
  • Exomes 𝑓: 0.049 (621 hom.)
• Consequence: PANK1 NM_148977.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 2 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]

MIR107 (HGNC:31496): (microRNA 107) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANK1	NM_148977.3	c.1200+287T>C		intron_variant	Intron 5 of 6	ENST00000307534.10	NP_683878.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANK1	ENST00000307534.10	c.1200+287T>C		intron_variant	Intron 5 of 6	1	NM_148977.3	ENSP00000302108.5
PANK1	ENST00000342512.4	c.936+287T>C		intron_variant	Intron 5 of 6	1		ENSP00000345118.3
PANK1	ENST00000322191.10	c.759+287T>C		intron_variant	Intron 4 of 5	1		ENSP00000318526.6
MIR107	ENST00000362127.2	n.-83T>C		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.0442 AC: 6723 AN: 152220 Hom.: 229 Cov.: 32

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0323

Gnomad ASJ AF: 0.0257

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.0592

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0713

Gnomad OTH AF: 0.0382

GnomAD4 exome AF: 0.0491 AC: 18388 AN: 374206 Hom.: 621 AF XY: 0.0464 AC XY: 9447 AN XY: 203764

African (AFR) AF: 0.0107 AC: 124 AN: 11602

American (AMR) AF: 0.0211 AC: 561 AN: 26546

Ashkenazi Jewish (ASJ) AF: 0.0235 AC: 263 AN: 11192

East Asian (EAS) AF: 0.00 AC: 0 AN: 18352

South Asian (SAS) AF: 0.0137 AC: 730 AN: 53364

European-Finnish (FIN) AF: 0.0579 AC: 1569 AN: 27082

Middle Eastern (MID) AF: 0.00546 AC: 17 AN: 3112

European-Non Finnish (NFE) AF: 0.0695 AC: 14162 AN: 203650

Other (OTH) AF: 0.0498 AC: 962 AN: 19306

GnomAD4 genome AF: 0.0441 AC: 6721 AN: 152338 Hom.: 229 Cov.: 32 AF XY: 0.0418 AC XY: 3110 AN XY: 74486

African (AFR) AF: 0.0107 AC: 445 AN: 41594

American (AMR) AF: 0.0323 AC: 494 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0257 AC: 89 AN: 3464

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.00787 AC: 38 AN: 4828

European-Finnish (FIN) AF: 0.0592 AC: 628 AN: 10616

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0713 AC: 4852 AN: 68018

Other (OTH) AF: 0.0378 AC: 80 AN: 2114

Alfa AF: 0.0637 Hom.: 323

Bravo AF: 0.0410

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.13
DANN	Benign	0.73
PhyloP100		-1.3
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: rs10509577; hg19: chr10-91352667;