chr12-6971024-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006331.8(EMG1):c.101C>G(p.Ala34Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0368 in 1,611,376 control chromosomes in the GnomAD database, including 1,281 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.028 ( 89 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1192 hom. )

Consequence

EMG1
NM_006331.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.22

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:

ENSG00000290146 (HGNC:):

ENSG00000290146 links:

PHB2 (HGNC:30306): (prohibitin 2) Enables several functions, including protein C-terminus binding activity; protein N-terminus binding activity; and protein dimerization activity. Involved in several processes, including defense response to virus; positive regulation of cell cycle phase transition; and regulation of transcription, DNA-templated. Located in several cellular components, including cell surface; mitochondrial membrane; and nuclear matrix. Part of mitochondrial prohibitin complex. [provided by Alliance of Genome Resources, Apr 2022]

PHB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019704998).

BP6

Variant 12-6971024-C-G is Benign according to our data. Variant chr12-6971024-C-G is described in ClinVar as [Benign]. Clinvar id is 218683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-6971024-C-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0285 (4334/152172) while in subpopulation NFE AF= 0.0402 (2731/68002). AF 95% confidence interval is 0.0389. There are 89 homozygotes in gnomad4. There are 2153 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 89 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMG1	NM_006331.8 link	c.101C>G	p.Ala34Gly	missense_variant	Exon 1 of 6	ENST00000599672.6	NP_006322.4	Q92979
EMG1	NM_001320049.2 link	c.101C>G	p.Ala34Gly	missense_variant	Exon 1 of 5		NP_001306978.1	Q92979
EMG1	NR_135131.2 link	n.112C>G		non_coding_transcript_exon_variant	Exon 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMG1	ENST00000599672.6 link	c.101C>G	p.Ala34Gly	missense_variant	Exon 1 of 6	1	NM_006331.8	ENSP00000470560.1		Q92979
ENSG00000290146	ENST00000607161.5 link	n.104C>G		non_coding_transcript_exon_variant	Exon 1 of 8	2		ENSP00000480420.1		A0A087WWQ2

Frequencies

GnomAD3 genomes

AF:

0.0285

AC:

4336

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00652

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0184

Gnomad ASJ

AF:

0.0239

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0102

Gnomad FIN

AF:

0.0801

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0402

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0301

AC:

7059

AN:

234174

Hom.:

149

AF XY:

0.0297

AC XY:

3776

AN XY:

127172

show subpopulations

Gnomad AFR exome

AF:

0.00600

Gnomad AMR exome

AF:

0.0128

Gnomad ASJ exome

AF:

0.0257

Gnomad EAS exome

AF:

0.0000591

Gnomad SAS exome

AF:

0.0109

Gnomad FIN exome

AF:

0.0772

Gnomad NFE exome

AF:

0.0401

Gnomad OTH exome

AF:

0.0321

GnomAD4 exome

AF:

0.0376

AC:

54889

AN:

1459204

Hom.:

1192

Cov.:

AF XY:

0.0367

AC XY:

26630

AN XY:

725624

show subpopulations

Gnomad4 AFR exome

AF:

0.00505

Gnomad4 AMR exome

AF:

0.0129

Gnomad4 ASJ exome

AF:

0.0260

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0104

Gnomad4 FIN exome

AF:

0.0752

Gnomad4 NFE exome

AF:

0.0418

Gnomad4 OTH exome

AF:

0.0357

GnomAD4 genome

AF:

0.0285

AC:

4334

AN:

152172

Hom.:

Cov.:

AF XY:

0.0289

AC XY:

2153

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.00650

Gnomad4 AMR

AF:

0.0184

Gnomad4 ASJ

AF:

0.0239

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00995

Gnomad4 FIN

AF:

0.0801

Gnomad4 NFE

AF:

0.0402

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.0340

Hom.:

Bravo

AF:

0.0231

TwinsUK

AF:

0.0448

AC:

166

ALSPAC

AF:

0.0423

AC:

163

ESP6500AA

AF:

0.00493

AC:

ESP6500EA

AF:

0.0398

AC:

328

ExAC

AF:

0.0285

AC:

3442

Asia WGS

AF:

0.00318

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 13, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.22

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0020

PrimateAI

Benign

0.40

Sift4G

Benign

0.22

Polyphen

0.0010

Vest4

0.16

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.36

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

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