Variant 12-6975083-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_006331.8(EMG1):c.413-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000651 in 1,613,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

EMG1
NM_006331.8 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001460

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.676

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 12-6975083-C-T is Benign according to our data. Variant chr12-6975083-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 720716.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
EMG1	NM_006331.8 linkuse as main transcript	c.413-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000599672.6
EMG1	NM_001320049.2 linkuse as main transcript	c.413-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
EMG1	NR_135131.2 linkuse as main transcript	n.424-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
EMG1	ENST00000599672.6 linkuse as main transcript	c.413-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006331.8	P1
EMG1	ENST00000539196.2 linkuse as main transcript	c.276-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2
EMG1	ENST00000611981.1 linkuse as main transcript	n.813C>T	non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000108

AC:

AN:

249256

Hom.:

AF XY:

0.0000592

AC XY:

AN XY:

135224

show subpopulations

Gnomad AFR exome

AF:

0.00174

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1461610

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.00125

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000388

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000416

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 21, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

Cadd

Benign

0.47

Dann

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000015

dbscSNV1_RF

Benign

0.0

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over