Genetic Variant MIR509-1:n.92A>C (chrX-147260534-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000385265.1(MIR509-1):n.92A>C variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. 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 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000037 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

MIR509-1
ENST00000385265.1 splice_region, non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.11

Publications

0 publications found

Variant links:

Genes affected

MIR509-1 (HGNC:32146): (microRNA 509-1) 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]

MIR509-1 links:

ENSG00000284377 (HGNC:):

ENSG00000284377 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
MIR509-1	NR_030236.1 link	n.92A>C	splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 1
LOC105373347	XR_005647083.2 link	n.208-8475T>G	intron_variant	Intron 2 of 3
LOC105373347	XR_005647084.2 link	n.158-8475T>G	intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
MIR509-1	ENST00000385265.1 link	n.92A>C	splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000284377	ENST00000639829.1 link	n.412-8475T>G	intron_variant	Intron 3 of 4	5
ENSG00000284377	ENST00000701574.2 link	n.209-8475T>G	intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.00000893

AC:

AN:

111956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000378

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000366

AC:

AN:

273389

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

108775

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

8367

American (AMR)

AF:

0.00

AC:

AN:

28736

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8717

East Asian (EAS)

AF:

0.00

AC:

AN:

9756

South Asian (SAS)

AF:

0.00

AC:

AN:

39943

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24329

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2106

European-Non Finnish (NFE)

AF:

0.00000719

AC:

AN:

139100

Other (OTH)

AF:

0.00

AC:

AN:

12335

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000893

AC:

AN:

111956

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34132

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30769

American (AMR)

AF:

0.00

AC:

AN:

10585

Ashkenazi Jewish (ASJ)

AF:

0.000378

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3540

South Asian (SAS)

AF:

0.00

AC:

AN:

2653

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6197

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53141

Other (OTH)

AF:

0.00

AC:

AN:

1505

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.6

(source)

DANN

Benign

0.80

PhyloP100

-2.1

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over