chr3-75630794-C-G

Variant names:

• chr3-75630794-C-G
• rs3008994
• ENST00000640185.1:n.32C>G

Variant summary

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

The ENST00000640185.1(MIR1324):​n.32C>G 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 (50 hom., cov: 62)
  • Exomes 𝑓: 0.25 (32 hom.)
  • Failed GnomAD Quality Control
• Consequence: MIR1324 ENST00000640185.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760
• Publications: 1 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=-0.71).
• BS2: High Homozygotes in GnomAdExome4 at 32 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR1324	NR_031714.1	n.32C>G		non_coding_transcript_exon_variant	Exon 1 of 1
CLUHP10		n.75630794C>G		intragenic_variant
MIR1324	unassigned_transcript_644	n.-29C>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR1324	ENST00000640185.1	n.32C>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000293315	ENST00000810254.1	n.231G>C		non_coding_transcript_exon_variant	Exon 2 of 4
ENSG00000293315	ENST00000810263.1	n.266G>C		non_coding_transcript_exon_variant	Exon 2 of 4

Frequencies

GnomAD3 genomes AF: 0.302 AC: 43547 AN: 143996 Hom.: 50 Cov.: 62

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.254 AC: 78634 AN: 309494 Hom.: 32 Cov.: 0 AF XY: 0.259 AC XY: 45145 AN XY: 174510

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

African (AFR) AF: 0.296 AC: 2388 AN: 8080

American (AMR) AF: 0.240 AC: 6620 AN: 27548

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 2054 AN: 8958

East Asian (EAS) AF: 0.395 AC: 4249 AN: 10756

South Asian (SAS) AF: 0.341 AC: 18256 AN: 53508

European-Finnish (FIN) AF: 0.165 AC: 4381 AN: 26560

Middle Eastern (MID) AF: 0.287 AC: 608 AN: 2122

European-Non Finnish (NFE) AF: 0.231 AC: 36635 AN: 158324

Other (OTH) AF: 0.252 AC: 3443 AN: 13638

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.302 AC: 43562 AN: 144102 Hom.: 50 Cov.: 62 AF XY: 0.303 AC XY: 21276 AN XY: 70246

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

African (AFR) AF: 0.345 AC: 13594 AN: 39360

American (AMR) AF: 0.288 AC: 4138 AN: 14368

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 949 AN: 3332

East Asian (EAS) AF: 0.425 AC: 2058 AN: 4840

South Asian (SAS) AF: 0.374 AC: 1697 AN: 4532

European-Finnish (FIN) AF: 0.225 AC: 2269 AN: 10092

Middle Eastern (MID) AF: 0.314 AC: 88 AN: 280

European-Non Finnish (NFE) AF: 0.277 AC: 17882 AN: 64468

Other (OTH) AF: 0.294 AC: 574 AN: 1954

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.9
DANN	Benign	0.31
PhyloP100		0.076
Mutation Taster		=98/2	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3008994; hg19: chr3-75679945;