rs34557733

Variant names:

• chr14-101026792-G-GA
• rs34557733
• XM_047432049.1:c.*5990dupA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The XM_047432049.1(LOC124903407):​c.*5990dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LOC124903407 XM_047432049.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

Genes affected

LOC124903407 (HGNC:):

MIR329-1 (HGNC:32050): (microRNA 329-1) 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]

MEG8 (HGNC:14574): (maternally expressed 8, small nucleolar RNA host gene) This gene is located in a cluster of imprinted genes on chromosome 14q32.3. It encodes a a non-protein coding transcript that is preferentially expressed from the maternal allele in skeletal muscle, and appears to be coordinately regulated with other imprinted genes in this region. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903407	XM_047432049.1	c.*5990dupA		3_prime_UTR_variant	Exon 5 of 5		XP_047288005.1
MIR329-1	NR_029967.1	n.10dupA		non_coding_transcript_exon_variant	Exon 1 of 1
MIR329-1	unassigned_transcript_2389	n.-5_-4insA		upstream_gene_variant
MIR329-1	unassigned_transcript_2390	n.-42_-41insA		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR329-1	ENST00000385028.3	n.10dupA		non_coding_transcript_exon_variant	Exon 1 of 1	6
MEG8	ENST00000636391.2	n.2086-552dupA		intron_variant	Intron 24 of 28	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34557733; hg19: chr14-101493129;