rs587776522

Variant names:

• chr7-129774757-C-T
• rs587776522
• ENST00000362288.1:n.13G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The ENST00000362288.1(MIR96):​n.13G>A variant causes a non coding transcript exon change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MIR96 ENST00000362288.1 non_coding_transcript_exon
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.27
• Publications: 2 publications found

Genes affected

MIR96 (HGNC:31648): (microRNA 96) 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]

ENSG00000304993 (HGNC:):

MIR183 (HGNC:31554): (microRNA 183) 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-129774757-C-T is Pathogenic according to our data. Variant chr7-129774757-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 865.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22). . Strength limited to SUPPORTING due to the PP5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000362288.1. 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
	MIR96	NR_029512.1		n.13G>A		non_coding_transcript_exon	Exon 1 of 1
	MIR183	NR_029615.1		n.*148G>A		downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR96	ENST00000362288.1	TSL:6	n.13G>A		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000304993	ENST00000807590.1		n.47C>T		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000286380	ENST00000710872.1		n.431+5033G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 320682 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 180732

African (AFR) AF: 0.00 AC: 0 AN: 8976

American (AMR) AF: 0.00 AC: 0 AN: 27434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10784

East Asian (EAS) AF: 0.00 AC: 0 AN: 9826

South Asian (SAS) AF: 0.00 AC: 0 AN: 59898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2776

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 158740

Other (OTH) AF: 0.00 AC: 0 AN: 14434

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 50 Pathogenic:1

May 01, 2009

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Benign	0.95
PhyloP100		7.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

Splicing

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

Other links and lift over

dbSNP: rs587776522; hg19: chr7-129414597;