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GeneBe

12-6970938-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_006331.8(EMG1):c.15T>C(p.Ser5=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,613,020 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 31 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 31 hom. )

Consequence

EMG1
NM_006331.8 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.208
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-6970938-T-C is Benign according to our data. Variant chr12-6970938-T-C is described in ClinVar as [Benign]. Clinvar id is 714059.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-6970938-T-C is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.208 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0113 (1722/152254) while in subpopulation AFR AF= 0.0388 (1610/41528). AF 95% confidence interval is 0.0372. There are 31 homozygotes in gnomad4. There are 810 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EMG1NM_006331.8 linkuse as main transcriptc.15T>C p.Ser5= synonymous_variant 1/6 ENST00000599672.6
EMG1NM_001320049.2 linkuse as main transcriptc.15T>C p.Ser5= synonymous_variant 1/5
EMG1NR_135131.2 linkuse as main transcriptn.26T>C non_coding_transcript_exon_variant 1/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EMG1ENST00000599672.6 linkuse as main transcriptc.15T>C p.Ser5= synonymous_variant 1/61 NM_006331.8 P1
EMG1ENST00000611981.1 linkuse as main transcriptn.26T>C non_coding_transcript_exon_variant 1/42
EMG1ENST00000620255.1 linkuse as main transcriptn.4T>C non_coding_transcript_exon_variant 1/22

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0112
AC:
1703
AN:
152138
Hom.:
29
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0384
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00465
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.0120
GnomAD3 exomes
AF:
0.00292
AC:
721
AN:
247118
Hom.:
14
AF XY:
0.00213
AC XY:
286
AN XY:
134084
show subpopulations
Gnomad AFR exome
AF:
0.0422
Gnomad AMR exome
AF:
0.00149
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000132
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000982
Gnomad OTH exome
AF:
0.00183
GnomAD4 exome
AF:
0.00127
AC:
1858
AN:
1460766
Hom.:
31
Cov.:
32
AF XY:
0.00107
AC XY:
778
AN XY:
726572
show subpopulations
Gnomad4 AFR exome
AF:
0.0395
Gnomad4 AMR exome
AF:
0.00209
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000230
Gnomad4 OTH exome
AF:
0.00278
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0113
AC:
1722
AN:
152254
Hom.:
31
Cov.:
32
AF XY:
0.0109
AC XY:
810
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.0388
Gnomad4 AMR
AF:
0.00464
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.0118
Alfa
AF:
0.00443
Hom.:
8
Bravo
AF:
0.0134
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000596

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
Cadd
Benign
5.7
Dann
Benign
0.63
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs149578211; hg19: chr12-7080101; API