rs11185776

Variant names:

• chr10-89592688-C-A
• rs11185776
• NM_148977.3:c.1200+509G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-89592688-C-A
• chr10-89592688-C-G

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+509G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 530,004 control chromosomes in the GnomAD database, including 274 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 0.031 (224 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (50 hom.)
• Consequence: PANK1 NM_148977.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.568
• Publications: 3 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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANK1	NM_148977.3	c.1200+509G>T		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+509G>T		intron_variant	Intron 5 of 6	1	NM_148977.3	ENSP00000302108.5
PANK1	ENST00000342512.4	c.936+509G>T		intron_variant	Intron 5 of 6	1		ENSP00000345118.3
PANK1	ENST00000322191.10	c.759+509G>T		intron_variant	Intron 4 of 5	1		ENSP00000318526.6
MIR107	ENST00000362127.2	n.*59G>T		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.0310 AC: 4723 AN: 152126 Hom.: 225 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0307

GnomAD4 exome AF: 0.00388 AC: 1466 AN: 377760 Hom.: 50 AF XY: 0.00288 AC XY: 618 AN XY: 214944

African (AFR) AF: 0.103 AC: 1072 AN: 10458

American (AMR) AF: 0.00605 AC: 216 AN: 35710

Ashkenazi Jewish (ASJ) AF: 0.000606 AC: 7 AN: 11552

East Asian (EAS) AF: 0.00 AC: 0 AN: 13090

South Asian (SAS) AF: 0.000227 AC: 15 AN: 66086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31772

Middle Eastern (MID) AF: 0.00389 AC: 11 AN: 2830

European-Non Finnish (NFE) AF: 0.000221 AC: 42 AN: 189702

Other (OTH) AF: 0.00622 AC: 103 AN: 16560

GnomAD4 genome AF: 0.0310 AC: 4725 AN: 152244 Hom.: 224 Cov.: 32 AF XY: 0.0297 AC XY: 2210 AN XY: 74434

African (AFR) AF: 0.106 AC: 4401 AN: 41536

American (AMR) AF: 0.0142 AC: 217 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000573 AC: 39 AN: 68020

Other (OTH) AF: 0.0304 AC: 64 AN: 2108

Alfa AF: 0.0464 Hom.: 149

Bravo AF: 0.0348

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.6
DANN	Benign	0.79
PhyloP100		-0.57
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: rs11185776; hg19: chr10-91352445;