chr16-1772946-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_023936.2(MRPS34):c.174G>C(p.Val58Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,445,350 control chromosomes in the GnomAD database, including 12,579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.097 ( 997 hom., cov: 35)

Exomes 𝑓: 0.13 ( 11582 hom. )

Consequence

MRPS34
NM_023936.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.73

Variant links:

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]

MRPS34 links:

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]

EME2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 16-1772946-C-G is Benign according to our data. Variant chr16-1772946-C-G is described in ClinVar as [Benign]. Clinvar id is 1275184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.73 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS34	NM_023936.2 link	c.174G>C	p.Val58Val	synonymous_variant	Exon 1 of 3	ENST00000397375.7	NP_076425.1	P82930
EME2	NM_001257370.2 link	c.-282C>G		5_prime_UTR_variant	Exon 1 of 8	ENST00000568449.7	NP_001244299.1	A4GXA9-1
MRPS34	NM_001300900.2 link	c.174G>C	p.Val58Val	synonymous_variant	Exon 1 of 3		NP_001287829.1	P82930C9JJ19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MRPS34	ENST00000397375.7 link	c.174G>C	p.Val58Val	synonymous_variant	Exon 1 of 3	1	NM_023936.2	ENSP00000380531.3	P82930
MRPS34	ENST00000177742.7 link	c.174G>C	p.Val58Val	synonymous_variant	Exon 1 of 3	1		ENSP00000177742.3	C9JJ19
EME2	ENST00000568449 link	c.-282C>G		5_prime_UTR_variant	Exon 1 of 8	1	NM_001257370.2	ENSP00000457353.1	A4GXA9-1

Frequencies

GnomAD3 genomes

AF:

0.0967

AC:

14718

AN:

152206

Hom.:

997

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0260

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.0996

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0482

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.232

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.111

GnomAD3 exomes

AF:

0.0935

AC:

4511

AN:

48254

Hom.:

285

AF XY:

0.0939

AC XY:

2504

AN XY:

26676

show subpopulations

Gnomad AFR exome

AF:

0.0222

Gnomad AMR exome

AF:

0.0782

Gnomad ASJ exome

AF:

0.171

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0423

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.108

GnomAD4 exome

AF:

0.127

AC:

164706

AN:

1293028

Hom.:

11582

Cov.:

AF XY:

0.126

AC XY:

79399

AN XY:

631970

show subpopulations

Gnomad4 AFR exome

AF:

0.0201

Gnomad4 AMR exome

AF:

0.0789

Gnomad4 ASJ exome

AF:

0.180

Gnomad4 EAS exome

AF:

0.000190

Gnomad4 SAS exome

AF:

0.0508

Gnomad4 FIN exome

AF:

0.115

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.0966

AC:

14708

AN:

152322

Hom.:

997

Cov.:

AF XY:

0.0940

AC XY:

7003

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0259

Gnomad4 AMR

AF:

0.0995

Gnomad4 ASJ

AF:

0.199

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0478

Gnomad4 FIN

AF:

0.119

Gnomad4 NFE

AF:

0.139

Gnomad4 OTH

AF:

0.110

Alfa

AF:

0.110

Hom.:

139

Bravo

AF:

0.0933

Asia WGS

AF:

0.0250

AC:

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 02, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

MRPS34-related disorder

Benign:1

Oct 29, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.91

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over