rs12975333

Variant names:

• chr19-51693275-G-T
• rs12975333
• ENST00000385273.1:n.22G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000385273.1(MIR125A):​n.22G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MIR125A ENST00000385273.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.79
• Publications: 29 publications found

Genes affected

MIR125A (HGNC:31505): (microRNA 125a) 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]

SPACA6-AS1 (HGNC:49383): (SPACA6 antisense RNA 1)

SPACA6 (HGNC:27113): (sperm acrosome associated 6) Predicted to be involved in fusion of sperm to egg plasma membrane involved in single fertilization. Predicted to be located in acrosomal vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPACA6	NM_001316972.2	c.-252G>T		upstream_gene_variant		ENST00000637797.2	NP_001303901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPACA6	ENST00000637797.2	c.-252G>T		upstream_gene_variant		1	NM_001316972.2	ENSP00000490829.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 580086 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 313452

African (AFR) AF: 0.00 AC: 0 AN: 16854

American (AMR) AF: 0.00 AC: 0 AN: 40782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19744

East Asian (EAS) AF: 0.00 AC: 0 AN: 34090

South Asian (SAS) AF: 0.00 AC: 0 AN: 65570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3976

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 318110

Other (OTH) AF: 0.00 AC: 0 AN: 30508

GnomAD4 genome Cov.: 32

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	-0.44
CADD	Benign	20
DANN	Benign	0.90
PhyloP100		2.8
PromoterAI		-0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Other links and lift over

dbSNP: rs12975333; hg19: chr19-52196528;