19-53725519-CTT-CTTT

Variant names:

• chr19-53725519-C-CT
• rs10583889
• ENST00000385190.1:n.81dupT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000385190.1(MIR516B2):​n.81dupT variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000272 in 367,500 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MIR516B2 ENST00000385190.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286
• Publications: 4 publications found

Genes affected

MIR516B2 (HGNC:32117): (microRNA 516b-2) 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]

ENSG00000269842 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000385190.1. 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
	MIR516B2	NR_030207.1		n.81dupT		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR516B2	ENST00000385190.1	TSL:6	n.81dupT		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000269842	ENST00000710708.1		n.585+12421dupT		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000413 AC: 1 AN: 242356 AF XY: 0.00000762

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000553

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000272 AC: 1 AN: 367500 Hom.: 0 Cov.: 0 AF XY: 0.00000481 AC XY: 1 AN XY: 207756

African (AFR) AF: 0.00 AC: 0 AN: 10212

American (AMR) AF: 0.00 AC: 0 AN: 35322

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11434

East Asian (EAS) AF: 0.0000786 AC: 1 AN: 12730

South Asian (SAS) AF: 0.00 AC: 0 AN: 64408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2804

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 182534

Other (OTH) AF: 0.00 AC: 0 AN: 16104

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10583889; hg19: chr19-54228773;