12-6975333-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_006331.8(EMG1):c.576C>T(p.Ser192=) 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, single submitter B:1
• Conservation: PhyloP100: 0.0930

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]

ACMG classification

Verdict is Benign. Variant got -15 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 id is 781063.Status of the report is criteria_provided_single_submitter, 1 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMG1	NM_006331.8	c.576C>T	p.Ser192=	synonymous_variant	5/6	ENST00000599672.6
EMG1	NM_001320049.2	c.471+185C>T		intron_variant
EMG1	NR_135131.2	n.587C>T		non_coding_transcript_exon_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMG1	ENST00000599672.6	c.576C>T	p.Ser192=	synonymous_variant	5/6	1	NM_006331.8	P1
EMG1	ENST00000539196.2	c.334+185C>T		intron_variant		2
EMG1	ENST00000611981.1	n.983C>T		non_coding_transcript_exon_variant	4/4	2

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

GnomAD3 exomes AF: 0.00531 AC: 1258 AN: 236766 Hom.: 32 AF XY: 0.00420 AC XY: 539 AN XY: 128248

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 SAS exome AF: 0.000102

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

Gnomad4 AFR exome AF: 0.0756

Gnomad4 AMR exome AF: 0.00326

Gnomad4 ASJ exome AF: 0.00956

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000938

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000226

Gnomad4 OTH exome AF: 0.00495

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

Gnomad4 AFR AF: 0.0684

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00510 Hom.: 26

Bravo AF: 0.0216

Asia WGS AF: 0.00433 AC: 16 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	7.9
Dann	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs34784123; hg19: chr12-7084495;