16-1772882-C-G

Variant names:

• chr16-1772882-C-G
• rs1394667548
• NM_023936.2:c.238G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_023936.2(MRPS34):​c.238G>C​(p.Val80Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V80V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MRPS34 NM_023936.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.07
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3334354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS34	NM_023936.2	c.238G>C	p.Val80Leu	missense_variant	Exon 1 of 3	ENST00000397375.7	NP_076425.1
EME2	NM_001257370.2	c.-346C>G		5_prime_UTR_variant	Exon 1 of 8	ENST00000568449.7	NP_001244299.1
MRPS34	NM_001300900.2	c.238G>C	p.Val80Leu	missense_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.238G>C	p.Val80Leu	missense_variant	Exon 1 of 3	1	NM_023936.2	ENSP00000380531.3
MRPS34	ENST00000177742.7	c.238G>C	p.Val80Leu	missense_variant	Exon 1 of 3	1		ENSP00000177742.3
EME2	ENST00000568449.7	c.-346C>G		5_prime_UTR_variant	Exon 1 of 8	1	NM_001257370.2	ENSP00000457353.1
MRPS34	ENST00000569585.1	n.-184G>C		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1299274 Hom.: 0 Cov.: 63 AF XY: 0.00 AC XY: 0 AN XY: 634390

African (AFR) AF: 0.00 AC: 0 AN: 27546

American (AMR) AF: 0.00 AC: 0 AN: 21606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19450

East Asian (EAS) AF: 0.00 AC: 0 AN: 33396

South Asian (SAS) AF: 0.00 AC: 0 AN: 66592

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4330

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1041474

Other (OTH) AF: 0.00 AC: 0 AN: 53992

GnomAD4 genome Cov.: 35

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Apr 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.238G>C (p.V80L) alteration is located in exon 1 (coding exon 1) of the MRPS34 gene. This alteration results from a G to C substitution at nucleotide position 238, causing the valine (V) at amino acid position 80 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	.;M
PhyloP100		2.1
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.085
Sift	Benign	0.034	D;D
Sift4G	Benign	0.17	T;T
Polyphen		0.89	P;P
Vest4		0.49
MutPred		0.47		Gain of catalytic residue at V80 (P = 0.0069);Gain of catalytic residue at V80 (P = 0.0069);
MVP		0.081
MPC		2.7
ClinPred		0.92	D
GERP RS		3.7
PromoterAI		-0.039	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.35
gMVP		0.66

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: rs1394667548; hg19: chr16-1822883;