chr16-1772829-G-A

Position:

• chr16-1772829-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6 BP7

The NM_023936.2(MRPS34):​c.291C>T​(p.Leu97=) 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. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: MRPS34 NM_023936.2 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.400

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 16-1772829-G-A is Benign according to our data. Variant chr16-1772829-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3061716.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.4 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPS34	NM_023936.2	c.291C>T	p.Leu97=	synonymous_variant	1/3	ENST00000397375.7
EME2	NM_001257370.2	c.-399G>A		5_prime_UTR_variant	1/8	ENST00000568449.7
MRPS34	NM_001300900.2	c.291C>T	p.Leu97=	synonymous_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPS34	ENST00000397375.7	c.291C>T	p.Leu97=	synonymous_variant	1/3	1	NM_023936.2	P1
MRPS34	ENST00000177742.7	c.291C>T	p.Leu97=	synonymous_variant	1/3	1
EME2	ENST00000568449.7	c.-399G>A		5_prime_UTR_variant	1/8	1	NM_001257370.2	P1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.00000232 AC: 3 AN: 1292916 Hom.: 0 Cov.: 63 AF XY: 0.00000159 AC XY: 1 AN XY: 628112

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000308

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000186

GnomAD4 genome Cov.: 35

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MRPS34-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 12, 2023

This variant is classified as likely 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	-0.58
CADD	Benign	11
DANN	Benign	0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs1416116979; hg19: chr16-1822830;