NM_148977.3:c.1200+304G>A

Variant names:

• chr10-89592893-C-T
• rs17481096
• NM_148977.3:c.1200+304G>A

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+304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0848 in 533,592 control chromosomes in the GnomAD database, including 2,246 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 0.074 (548 hom., cov: 32)
  • Exomes 𝑓: 0.089 (1698 hom.)
• Consequence: PANK1 NM_148977.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421
• Publications: 5 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=-0.51).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANK1	NM_148977.3	MANE Select	c.1200+304G>A		intron	N/A	NP_683878.2
	PANK1	NM_148978.3		c.936+304G>A		intron	N/A	NP_683879.1
	PANK1	NM_138316.4		c.759+304G>A		intron	N/A	NP_612189.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANK1	ENST00000307534.10	TSL:1 MANE Select	c.1200+304G>A		intron	N/A	ENSP00000302108.5
	PANK1	ENST00000342512.4	TSL:1	c.936+304G>A		intron	N/A	ENSP00000345118.3
	PANK1	ENST00000322191.10	TSL:1	c.759+304G>A		intron	N/A	ENSP00000318526.6

Frequencies

GnomAD3 genomes AF: 0.0742 AC: 11297 AN: 152198 Hom.: 541 Cov.: 32

Gnomad AFR AF: 0.0200

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.0752

Gnomad FIN AF: 0.0678

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0693

GnomAD4 exome AF: 0.0890 AC: 33921 AN: 381276 Hom.: 1698 AF XY: 0.0895 AC XY: 18798 AN XY: 210088

African (AFR) AF: 0.0193 AC: 226 AN: 11684

American (AMR) AF: 0.123 AC: 3747 AN: 30354

Ashkenazi Jewish (ASJ) AF: 0.0709 AC: 804 AN: 11340

East Asian (EAS) AF: 0.0149 AC: 255 AN: 17082

South Asian (SAS) AF: 0.0879 AC: 5046 AN: 57410

European-Finnish (FIN) AF: 0.0665 AC: 1937 AN: 29112

Middle Eastern (MID) AF: 0.0907 AC: 278 AN: 3064

European-Non Finnish (NFE) AF: 0.0992 AC: 20080 AN: 202458

Other (OTH) AF: 0.0825 AC: 1548 AN: 18772

GnomAD4 genome AF: 0.0742 AC: 11306 AN: 152316 Hom.: 548 Cov.: 32 AF XY: 0.0732 AC XY: 5454 AN XY: 74466

African (AFR) AF: 0.0200 AC: 831 AN: 41570

American (AMR) AF: 0.108 AC: 1659 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0755 AC: 262 AN: 3470

East Asian (EAS) AF: 0.0212 AC: 110 AN: 5184

South Asian (SAS) AF: 0.0750 AC: 362 AN: 4826

European-Finnish (FIN) AF: 0.0678 AC: 719 AN: 10604

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7136 AN: 68034

Other (OTH) AF: 0.0686 AC: 145 AN: 2114

Alfa AF: 0.0896 Hom.: 116

Bravo AF: 0.0741

Asia WGS AF: 0.0520 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17481096; hg19: chr10-91352650;