EMG1 p.Ser192Arg

Variant names:

• chr12-6975331-A-C
• NM_006331.8:c.574A>C
• EMG1 p.Ser192Arg

Your query was ambiguous. Multiple possible variants found:

• chr12-6975331-A-C
• chr12-6975333-C-A
• chr12-6975333-C-G
• chr12-6975331-AGC-CGT
• chr12-6975331-AGC-CGA
• chr12-6975331-AGC-CGG

Variant summary

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

The NM_006331.8(EMG1):​c.574A>C​(p.Ser192Arg) 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 benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S192S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EMG1 NM_006331.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 0 publications found

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]

EMG1 Gene-Disease associations (from GenCC):

• Bowen-Conradi syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics, Orphanet

ENSG00000290146 (HGNC:):

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 (MetaRNN=0.17853552).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006331.8. 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
	EMG1	NM_006331.8	MANE Select	c.574A>C	p.Ser192Arg	missense	Exon 5 of 6	NP_006322.4
	EMG1	NM_001320049.2		c.471+183A>C		intron	N/A	NP_001306978.1
	EMG1	NR_135131.2		n.585A>C		non_coding_transcript_exon	Exon 5 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMG1	ENST00000599672.6	TSL:1 MANE Select	c.574A>C	p.Ser192Arg	missense	Exon 5 of 6	ENSP00000470560.1	Q92979
	ENSG00000290146	ENST00000607161.5	TSL:2	n.577A>C		non_coding_transcript_exon	Exon 5 of 8	ENSP00000480420.1	A0A087WWQ2
	EMG1	ENST00000960685.1		c.688A>C	p.Ser230Arg	missense	Exon 6 of 7	ENSP00000630744.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.18	T
PhyloP100		1.4
PrimateAI	Benign	0.43	T
Sift4G	Benign	0.36	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.26
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-7084493;