Genetic Variant EMG1:p.Asp86Asp (chr12-6974428-T-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_006331.8(EMG1):c.258T>C(p.Asp86Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

EMG1
NM_006331.8 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.56

Publications

0 publications found

Variant links:

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)

EMG1 links:

ENSG00000290146 (HGNC:):

ENSG00000290146 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 12-6974428-T-C is Benign according to our data. Variant chr12-6974428-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 738778.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.56 with no splicing effect.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EMG1	NM_006331.8	MANE Select	c.258T>C	p.Asp86Asp	synonymous	Exon 2 of 6	NP_006322.4
EMG1	NM_001320049.2		c.258T>C	p.Asp86Asp	synonymous	Exon 2 of 5	NP_001306978.1
EMG1	NR_135131.2		n.269T>C		non_coding_transcript_exon	Exon 2 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EMG1	ENST00000599672.6	TSL:1 MANE Select	c.258T>C	p.Asp86Asp	synonymous	Exon 2 of 6	ENSP00000470560.1	Q92979
ENSG00000290146	ENST00000607161.5	TSL:2	n.261T>C		non_coding_transcript_exon	Exon 2 of 8	ENSP00000480420.1	A0A087WWQ2
EMG1	ENST00000960685.1		c.372T>C	p.Asp124Asp	synonymous	Exon 3 of 7	ENSP00000630744.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000161

AC:

AN:

248768

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000167

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461384

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726966

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.000101

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111634

Other (OTH)

AF:

0.000166

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

8.8

(source)

DANN

Benign

0.88

PhyloP100

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over