rs3008993

Variant names:

• chr3-75630855-T-C
• rs3008993
• ENST00000640185.1:n.93T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000640185.1(MIR1324):​n.93T>C variant causes a 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 0.30 (34 hom., cov: 65)
  • Exomes 𝑓: 0.26 (35 hom.)
  • Failed GnomAD Quality Control
• Consequence: MIR1324 ENST00000640185.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 2 publications found

Genes affected

MIR1324 (HGNC:35377): (microRNA 1324) 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]

ENSG00000293315 (HGNC:):

CLUHP10 (HGNC:51574): (clustered mitochondria homolog pseudogene 10)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BS2: High Homozygotes in GnomAdExome4 at 35 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR1324	NR_031714.1	n.93T>C		non_coding_transcript_exon_variant	Exon 1 of 1
CLUHP10		n.75630855T>C		intragenic_variant
MIR1324	unassigned_transcript_644	n.*9T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR1324	ENST00000640185.1	n.93T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000293315	ENST00000810254.1	n.170A>G		non_coding_transcript_exon_variant	Exon 2 of 4
ENSG00000293315	ENST00000810263.1	n.205A>G		non_coding_transcript_exon_variant	Exon 2 of 4

Frequencies

GnomAD3 genomes AF: 0.301 AC: 41942 AN: 139478 Hom.: 34 Cov.: 65

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.297

GnomAD4 exome AF: 0.259 AC: 80041 AN: 309326 Hom.: 35 Cov.: 0 AF XY: 0.264 AC XY: 45967 AN XY: 174176

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

African (AFR) AF: 0.314 AC: 2557 AN: 8146

American (AMR) AF: 0.247 AC: 6818 AN: 27604

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 2141 AN: 9088

East Asian (EAS) AF: 0.398 AC: 4255 AN: 10692

South Asian (SAS) AF: 0.352 AC: 18731 AN: 53278

European-Finnish (FIN) AF: 0.159 AC: 4158 AN: 26206

Middle Eastern (MID) AF: 0.302 AC: 638 AN: 2116

European-Non Finnish (NFE) AF: 0.235 AC: 37252 AN: 158558

Other (OTH) AF: 0.256 AC: 3491 AN: 13638

⚠️ 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.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.301 AC: 41960 AN: 139574 Hom.: 34 Cov.: 65 AF XY: 0.301 AC XY: 20475 AN XY: 67976

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

African (AFR) AF: 0.354 AC: 13517 AN: 38186

American (AMR) AF: 0.283 AC: 3921 AN: 13864

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 911 AN: 3242

East Asian (EAS) AF: 0.422 AC: 1985 AN: 4702

South Asian (SAS) AF: 0.377 AC: 1634 AN: 4336

European-Finnish (FIN) AF: 0.214 AC: 2082 AN: 9720

Middle Eastern (MID) AF: 0.313 AC: 85 AN: 272

European-Non Finnish (NFE) AF: 0.272 AC: 16977 AN: 62522

Other (OTH) AF: 0.294 AC: 558 AN: 1896

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.305 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.32
PhyloP100		0.062
Mutation Taster		=97/3	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3008993; hg19: chr3-75680006;