NM_001257370.2:c.-261C>T

Variant names:

• chr16-1772967-C-T
• rs749789584
• NM_001257370.2:c.-261C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001257370.2(EME2):​c.-261C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000166 in 1,447,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 35)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: EME2 NM_001257370.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.18
• Publications: 0 publications found

Genes affected

EME2 (HGNC:27289): (essential meiotic structure-specific endonuclease subunit 2) EME2 forms a heterodimer with MUS81 (MIM 606591) that functions as an XPF (MIM 278760)-type flap/fork endonuclease in DNA repair (Ciccia et al., 2007 [PubMed 17289582]).[supplied by OMIM, Mar 2008]

MRPS34 (HGNC:16618): (mitochondrial ribosomal protein S34) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 28S subunit protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

MRPS34 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation deficiency 32

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 16-1772967-C-T is Benign according to our data. Variant chr16-1772967-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1373338.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257370.2. 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
	EME2	NM_001257370.2	MANE Select	c.-261C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001244299.1	A4GXA9-1
	MRPS34	NM_023936.2	MANE Select	c.153G>A	p.Pro51Pro	synonymous	Exon 1 of 3	NP_076425.1	P82930
	EME2	NM_001257370.2	MANE Select	c.-261C>T		5_prime_UTR	Exon 1 of 8	NP_001244299.1	A4GXA9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EME2	ENST00000568449.7	TSL:1 MANE Select	c.-261C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000457353.1	A4GXA9-1
	MRPS34	ENST00000397375.7	TSL:1 MANE Select	c.153G>A	p.Pro51Pro	synonymous	Exon 1 of 3	ENSP00000380531.3	P82930
	MRPS34	ENST00000177742.7	TSL:1	c.153G>A	p.Pro51Pro	synonymous	Exon 1 of 3	ENSP00000177742.3	C9JJ19

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152248 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.000362

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

GnomAD2 exomes AF: 0.0000198 AC: 1 AN: 50486 AF XY: 0.00

Gnomad AFR exome AF: 0.00124

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000695 AC: 9 AN: 1294812 Hom.: 0 Cov.: 64 AF XY: 0.00000948 AC XY: 6 AN XY: 633058

African (AFR) AF: 0.000158 AC: 4 AN: 25240

American (AMR) AF: 0.00 AC: 0 AN: 20194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19354

East Asian (EAS) AF: 0.00 AC: 0 AN: 30754

South Asian (SAS) AF: 0.00 AC: 0 AN: 65684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4990

European-Non Finnish (NFE) AF: 0.00000386 AC: 4 AN: 1035054

Other (OTH) AF: 0.0000187 AC: 1 AN: 53408

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152248 Hom.: 0 Cov.: 35 AF XY: 0.0000538 AC XY: 4 AN XY: 74390

African (AFR) AF: 0.000362 AC: 15 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000471 Hom.: 0

Bravo AF: 0.0000869

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.9
DANN	Benign	0.91
PhyloP100		-2.2
PromoterAI		-0.0042	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7

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

Other links and lift over

dbSNP: rs749789584; hg19: chr16-1822968;