NM_023936.2:c.174G>A

Variant names:

• chr16-1772946-C-T
• rs1076695
• NM_023936.2:c.174G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_023936.2(MRPS34):​c.174G>A​(p.Val58Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000464 in 1,293,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V58V) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: MRPS34 NM_023936.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 0 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023936.2. 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
	MRPS34	NM_023936.2	MANE Select	c.174G>A	p.Val58Val	synonymous	Exon 1 of 3	NP_076425.1	P82930
	EME2	NM_001257370.2	MANE Select	c.-282C>T		5_prime_UTR	Exon 1 of 8	NP_001244299.1	A4GXA9-1
	MRPS34	NM_001300900.2		c.174G>A	p.Val58Val	synonymous	Exon 1 of 3	NP_001287829.1	C9JJ19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS34	ENST00000397375.7	TSL:1 MANE Select	c.174G>A	p.Val58Val	synonymous	Exon 1 of 3	ENSP00000380531.3	P82930
	MRPS34	ENST00000177742.7	TSL:1	c.174G>A	p.Val58Val	synonymous	Exon 1 of 3	ENSP00000177742.3	C9JJ19
	EME2	ENST00000568449.7	TSL:1 MANE Select	c.-282C>T		5_prime_UTR	Exon 1 of 8	ENSP00000457353.1	A4GXA9-1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.00000464 AC: 6 AN: 1293234 Hom.: 0 Cov.: 67 AF XY: 0.00000475 AC XY: 3 AN XY: 632064

African (AFR) AF: 0.00 AC: 0 AN: 25364

American (AMR) AF: 0.00 AC: 0 AN: 19528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18866

East Asian (EAS) AF: 0.00 AC: 0 AN: 31528

South Asian (SAS) AF: 0.0000154 AC: 1 AN: 64928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4714

European-Non Finnish (NFE) AF: 0.00000386 AC: 4 AN: 1037148

Other (OTH) AF: 0.0000187 AC: 1 AN: 53372

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Uncertain	0.98
PhyloP100		1.7
PromoterAI		0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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: rs1076695; hg19: chr16-1822947;