NM_023936.2:c.291C>G

Variant names:

• chr16-1772829-G-C
• rs1416116979
• NM_023936.2:c.291C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_023936.2(MRPS34):​c.291C>G​(p.Leu97Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000232 in 1,292,916 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. L97L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: MRPS34 NM_023936.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=0.4 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS34	NM_023936.2	c.291C>G	p.Leu97Leu	synonymous_variant	Exon 1 of 3	ENST00000397375.7	NP_076425.1
EME2	NM_001257370.2	c.-399G>C		5_prime_UTR_variant	Exon 1 of 8	ENST00000568449.7	NP_001244299.1
MRPS34	NM_001300900.2	c.291C>G	p.Leu97Leu	synonymous_variant	Exon 1 of 3		NP_001287829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS34	ENST00000397375.7	c.291C>G	p.Leu97Leu	synonymous_variant	Exon 1 of 3	1	NM_023936.2	ENSP00000380531.3
MRPS34	ENST00000177742.7	c.291C>G	p.Leu97Leu	synonymous_variant	Exon 1 of 3	1		ENSP00000177742.3
EME2	ENST00000568449.7	c.-399G>C		5_prime_UTR_variant	Exon 1 of 8	1	NM_001257370.2	ENSP00000457353.1
MRPS34	ENST00000569585.1	n.-131C>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD2 exomes AF: 0.0000156 AC: 1 AN: 64150 AF XY: 0.0000305

Gnomad AFR exome AF: 0.00

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: 0.00000232 AC: 3 AN: 1292916 Hom.: 0 Cov.: 63 AF XY: 0.00000318 AC XY: 2 AN XY: 628112

African (AFR) AF: 0.00 AC: 0 AN: 28618

American (AMR) AF: 0.00 AC: 0 AN: 21506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19126

East Asian (EAS) AF: 0.00 AC: 0 AN: 34824

South Asian (SAS) AF: 0.0000154 AC: 1 AN: 64838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3892

European-Non Finnish (NFE) AF: 9.65e-7 AC: 1 AN: 1036096

Other (OTH) AF: 0.0000186 AC: 1 AN: 53758

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.3
DANN	Benign	0.88
PhyloP100		0.40
PromoterAI		0.070	Neutral

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: rs1416116979; hg19: chr16-1822830;