rs181590179

chr16-368381-C-Gchr16-368381-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006428.5(MRPL28):c.610G>C(p.Val204Leu) 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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V204M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: MRPL28 NM_006428.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.13

Genes affected

MRPL28 (HGNC:14484): (mitochondrial ribosomal protein L28) 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 39S subunit protein, a part of which was originally isolated by its ability to recognize tyrosinase in an HLA-A24-restricted fashion. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29518956).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL28	NM_006428.5	c.610G>C	p.Val204Leu	missense_variant	5/6	ENST00000199706.13
MRPL28	XM_005255041.3	c.610G>C	p.Val204Leu	missense_variant	5/6
MRPL28	XM_011522351.3	c.610G>C	p.Val204Leu	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL28	ENST00000199706.13	c.610G>C	p.Val204Leu	missense_variant	5/6	1	NM_006428.5	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
Cadd	Benign	21
Dann	Benign	0.96
DEOGEN2	Benign	0.093	T;T;T;T;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.30	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.9	M;M;M;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.49	T
Polyphen		0.15	B;B;B;.;.
Vest4		0.32
MutPred		0.41		Gain of disorder (P = 0.0843);Gain of disorder (P = 0.0843);Gain of disorder (P = 0.0843);Gain of disorder (P = 0.0843);Gain of disorder (P = 0.0843);
MVP		0.19
ClinPred		0.96	D
GERP RS		3.5
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.35
gMVP		0.51

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

Other links and lift over

dbSNP: rs181590179; hg19: chr16-418381;