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GeneBe

12-6975270-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.513T>C(p.Cys171=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,613,564 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0022 ( 64 hom. )

Consequence

EMG1
NM_006331.8 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.851
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=-0.59).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-6975270-T-C is Benign according to our data. Variant chr12-6975270-T-C is described in ClinVar as [Benign]. Clinvar id is 726527.Status of the report is criteria_provided_single_submitter, 1 stars.
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=0.851 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00169 (258/152372) while in subpopulation SAS AF= 0.0308 (149/4830). AF 95% confidence interval is 0.0268. There are 1 homozygotes in gnomad4. There are 159 alleles in male gnomad4 subpopulation. Median coverage is 33. 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 GnomAdExome4 at 64 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EMG1NM_006331.8 linkuse as main transcriptc.513T>C p.Cys171= synonymous_variant 5/6 ENST00000599672.6
EMG1NM_001320049.2 linkuse as main transcriptc.471+122T>C intron_variant
EMG1NR_135131.2 linkuse as main transcriptn.524T>C non_coding_transcript_exon_variant 5/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EMG1ENST00000599672.6 linkuse as main transcriptc.513T>C p.Cys171= synonymous_variant 5/61 NM_006331.8 P1
EMG1ENST00000539196.2 linkuse as main transcriptc.334+122T>C intron_variant 2
EMG1ENST00000611981.1 linkuse as main transcriptn.920T>C non_coding_transcript_exon_variant 4/42

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00170
AC:
259
AN:
152254
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000555
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0146
Gnomad SAS
AF:
0.0312
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00494
AC:
1225
AN:
247770
Hom.:
25
AF XY:
0.00570
AC XY:
766
AN XY:
134484
show subpopulations
Gnomad AFR exome
AF:
0.000847
Gnomad AMR exome
AF:
0.0000873
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0157
Gnomad SAS exome
AF:
0.0294
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000446
Gnomad OTH exome
AF:
0.00465
GnomAD4 exome
AF:
0.00217
AC:
3169
AN:
1461192
Hom.:
64
Cov.:
32
AF XY:
0.00275
AC XY:
1996
AN XY:
726836
show subpopulations
Gnomad4 AFR exome
AF:
0.000418
Gnomad4 AMR exome
AF:
0.0000672
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0150
Gnomad4 SAS exome
AF:
0.0257
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000387
Gnomad4 OTH exome
AF:
0.00484
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00169
AC:
258
AN:
152372
Hom.:
1
Cov.:
33
AF XY:
0.00213
AC XY:
159
AN XY:
74520
show subpopulations
Gnomad4 AFR
AF:
0.000553
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0146
Gnomad4 SAS
AF:
0.0308
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00106
Hom.:
2
Bravo
AF:
0.00100
Asia WGS
AF:
0.0250
AC:
86
AN:
3478

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
-0.59
Cadd
Benign
9.0
Dann
Benign
0.79
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs139761201; hg19: chr12-7084432; COSMIC: COSV54641390; COSMIC: COSV54641390; API