chr12-6975333-C-T

Variant names:

• chr12-6975333-C-T
• rs34784123
• NM_006331.8:c.576C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006331.8(EMG1):​c.576C>T​(p.Ser192Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00405 in 1,607,664 control chromosomes in the GnomAD database, including 207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (107 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (100 hom.)
• Consequence: EMG1 NM_006331.8 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0930
• Publications: 7 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: ClinGen, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000290146 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 12-6975333-C-T is Benign according to our data. Variant chr12-6975333-C-T is described in ClinVar as Benign. ClinVar VariationId is 781063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.093 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0663 is higher than 0.05.

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.576C>T	p.Ser192Ser	synonymous	Exon 5 of 6	NP_006322.4
	EMG1	NM_001320049.2		c.471+185C>T		intron	N/A	NP_001306978.1
	EMG1	NR_135131.2		n.587C>T		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.576C>T	p.Ser192Ser	synonymous	Exon 5 of 6	ENSP00000470560.1	Q92979
	ENSG00000290146	ENST00000607161.5	TSL:2	n.579C>T		non_coding_transcript_exon	Exon 5 of 8	ENSP00000480420.1	A0A087WWQ2
	EMG1	ENST00000960685.1		c.690C>T	p.Ser230Ser	synonymous	Exon 6 of 7	ENSP00000630744.1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 3004 AN: 152248 Hom.: 106 Cov.: 33

Gnomad AFR AF: 0.0684

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00549

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.00531 AC: 1258 AN: 236766 AF XY: 0.00420

Gnomad AFR exome AF: 0.0679

Gnomad AMR exome AF: 0.00295

Gnomad ASJ exome AF: 0.0115

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000395

Gnomad OTH exome AF: 0.00289

GnomAD4 exome AF: 0.00241 AC: 3504 AN: 1455298 Hom.: 100 Cov.: 32 AF XY: 0.00210 AC XY: 1517 AN XY: 723282

African (AFR) AF: 0.0756 AC: 2524 AN: 33402

American (AMR) AF: 0.00326 AC: 142 AN: 43516

Ashkenazi Jewish (ASJ) AF: 0.00956 AC: 248 AN: 25932

East Asian (EAS) AF: 0.00 AC: 0 AN: 39576

South Asian (SAS) AF: 0.0000938 AC: 8 AN: 85290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53092

Middle Eastern (MID) AF: 0.00590 AC: 34 AN: 5760

European-Non Finnish (NFE) AF: 0.000226 AC: 250 AN: 1108548

Other (OTH) AF: 0.00495 AC: 298 AN: 60182

GnomAD4 genome AF: 0.0198 AC: 3014 AN: 152366 Hom.: 107 Cov.: 33 AF XY: 0.0196 AC XY: 1461 AN XY: 74512

African (AFR) AF: 0.0684 AC: 2844 AN: 41580

American (AMR) AF: 0.00549 AC: 84 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68040

Other (OTH) AF: 0.0147 AC: 31 AN: 2114

Alfa AF: 0.00683 Hom.: 77

Bravo AF: 0.0216

Asia WGS AF: 0.00433 AC: 16 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.9
DANN	Benign	0.83
PhyloP100		0.093
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs34784123; hg19: chr12-7084495;