XM_047432049.1:c.*3004C>T

Variant names:

• chr14-101023808-C-T
• rs41286566
• XM_047432049.1:c.*3004C>T

Variant summary

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

The XM_047432049.1(LOC124903407):​c.*3004C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000529 in 529,622 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: LOC124903407 XM_047432049.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.989
• Publications: 7 publications found

Genes affected

LOC124903407 (HGNC:):

MIR299 (HGNC:31618): (microRNA 299) 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

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=-0.22).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000385016.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR299	NR_029841.1		n.15C>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR299	ENST00000385016.4	TSL:6	n.15C>T		non_coding_transcript_exon	Exon 1 of 1
	MEG8	ENST00000636391.2	TSL:5	n.2086-3538C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

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

GnomAD2 exomes AF: 0.0000406 AC: 10 AN: 246462 AF XY: 0.0000300

Gnomad AFR exome AF: 0.0000623

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000717

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000662 AC: 25 AN: 377442 Hom.: 0 Cov.: 0 AF XY: 0.0000512 AC XY: 11 AN XY: 214850

African (AFR) AF: 0.00 AC: 0 AN: 10274

American (AMR) AF: 0.00 AC: 0 AN: 35416

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11660

East Asian (EAS) AF: 0.00 AC: 0 AN: 13144

South Asian (SAS) AF: 0.0000611 AC: 4 AN: 65432

European-Finnish (FIN) AF: 0.0000313 AC: 1 AN: 31940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2048

European-Non Finnish (NFE) AF: 0.0000995 AC: 19 AN: 191032

Other (OTH) AF: 0.0000606 AC: 1 AN: 16496

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152180 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74348

African (AFR) AF: 0.0000483 AC: 2 AN: 41428

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Benign	0.92
PhyloP100		0.99

Splicing

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

Other links and lift over

dbSNP: rs41286566; hg19: chr14-101490145;