12-6970938-T-C

Variant names:

• chr12-6970938-T-C
• rs149578211
• NM_006331.8:c.15T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006331.8(EMG1):​c.15T>C​(p.Ser5Ser) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.208
• Publications: 0 publications found

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]

ENSG00000290146 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 12-6970938-T-C is Benign according to our data. Variant chr12-6970938-T-C is described in ClinVar as Benign. ClinVar VariationId is 714059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.208 with no splicing effect.
• BS1: 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 31 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMG1	NM_006331.8	MANE Select	c.15T>C	p.Ser5Ser	synonymous	Exon 1 of 6	NP_006322.4
	EMG1	NM_001320049.2		c.15T>C	p.Ser5Ser	synonymous	Exon 1 of 5	NP_001306978.1
	EMG1	NR_135131.2		n.26T>C		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMG1	ENST00000599672.6	TSL:1 MANE Select	c.15T>C	p.Ser5Ser	synonymous	Exon 1 of 6	ENSP00000470560.1	Q92979
	ENSG00000290146	ENST00000607161.5	TSL:2	n.18T>C		non_coding_transcript_exon	Exon 1 of 8	ENSP00000480420.1	A0A087WWQ2
	EMG1	ENST00000960685.1		c.15T>C	p.Ser5Ser	synonymous	Exon 1 of 7	ENSP00000630744.1

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1703 AN: 152138 Hom.: 29 Cov.: 32

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

GnomAD2 exomes AF: 0.00292 AC: 721 AN: 247118 AF XY: 0.00213

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 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

African (AFR) AF: 0.0395 AC: 1323 AN: 33462

American (AMR) AF: 0.00209 AC: 93 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.000230 AC: 256 AN: 1111454

Other (OTH) AF: 0.00278 AC: 168 AN: 60338

GnomAD4 genome AF: 0.0113 AC: 1722 AN: 152254 Hom.: 31 Cov.: 32 AF XY: 0.0109 AC XY: 810 AN XY: 74442

African (AFR) AF: 0.0388 AC: 1610 AN: 41528

American (AMR) AF: 0.00464 AC: 71 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68024

Other (OTH) AF: 0.0118 AC: 25 AN: 2112

Alfa AF: 0.00469 Hom.: 8

Bravo AF: 0.0134

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000596

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.7
DANN	Benign	0.63
PhyloP100		0.21
PromoterAI		0.061	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs149578211; hg19: chr12-7080101;