16-1772300-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_023936.2(MRPS34):c.578T>C(p.Val193Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MRPS34 NM_023936.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.44

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12028071).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPS34	NM_023936.2	c.578T>C	p.Val193Ala	missense_variant	3/3	ENST00000397375.7
MRPS34	NM_001300900.2	c.599T>C	p.Val200Ala	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPS34	ENST00000397375.7	c.578T>C	p.Val193Ala	missense_variant	3/3	1	NM_023936.2	P1
MRPS34	ENST00000177742.7	c.599T>C	p.Val200Ala	missense_variant	3/3	1
MRPS34	ENST00000569585.1	n.309T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2023

The c.578T>C (p.V193A) alteration is located in exon 3 (coding exon 3) of the MRPS34 gene. This alteration results from a T to C substitution at nucleotide position 578, causing the valine (V) at amino acid position 193 to be replaced by an alanine (A). 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	0.18
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	21
Dann	Benign	0.81
DEOGEN2	Benign	0.035	T;T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.54	T;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.029	B;B
Vest4		0.16
MutPred		0.37		Gain of disorder (P = 0.0443);.;
MVP		0.061
MPC		0.20
ClinPred		0.56	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-1822301;