12-6971049-G-T

Position:

• chr12-6971049-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006331.8(EMG1):​c.126G>T​(p.Arg42Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EMG1 NM_006331.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34

Genes affected

EMG1 (HGNC:16912): (EMG1 N1-specific pseudouridine methyltransferase) This gene encodes an essential, conserved eukaryotic protein that methylates pseudouridine in 18S rRNA. The related protein in yeast is a component of the small subunit processome and is essential for biogenesis of the ribosomal 40S subunit. A mutation in this gene has been associated with Bowen-Conradi syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ENSG00000290146 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.829

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMG1	NM_006331.8	c.126G>T	p.Arg42Ser	missense_variant	1/6	ENST00000599672.6	NP_006322.4
EMG1	NM_001320049.2	c.126G>T	p.Arg42Ser	missense_variant	1/5		NP_001306978.1
EMG1	NR_135131.2	n.137G>T		non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMG1	ENST00000599672.6	c.126G>T	p.Arg42Ser	missense_variant	1/6	1	NM_006331.8	ENSP00000470560.1
ENSG00000290146	ENST00000607161.5	n.129G>T		non_coding_transcript_exon_variant	1/8	2		ENSP00000480420.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
CADD	Uncertain	25
DEOGEN2	Benign	0.26	T
LIST_S2	Pathogenic	0.98	D
MetaRNN	Pathogenic	0.83	D
Sift4G	Uncertain	0.016	D
Vest4		0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17857448; hg19: -;