2-99186226-T-G

Position:

• chr2-99186226-T-G

Variant summary

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

The ENST00000338148.8(MRPL30):​c.23T>G​(p.Val8Gly) 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. 16/21 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: MRPL30 ENST00000338148.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.05

Genes affected

MRPL30 (HGNC:14036): (mitochondrial ribosomal protein L30) 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. Alternative splicing results in multiple transcript variants. Pseudogenes corresponding to this gene are found on chromosomes 6p and 12p. Read-through transcription also exists between this gene and the neighboring upstream lipoyltransferase 1 (LIPT1) gene. [provided by RefSeq, Mar 2011]

ENSG00000273155 (HGNC:):

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=0.12725544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL30	NM_145212.4	c.23T>G	p.Val8Gly	missense_variant	2/6	ENST00000338148.8	NP_660213.1
MRPL30	NR_028356.2	n.116T>G		non_coding_transcript_exon_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL30	ENST00000338148.8	c.23T>G	p.Val8Gly	missense_variant	2/6	1	NM_145212.4	ENSP00000338057.3
ENSG00000273155	ENST00000410042.1	c.23T>G	p.Val8Gly	missense_variant	3/6	2		ENSP00000387111.1
ENSG00000241962	ENST00000424491.5	n.113T>G		non_coding_transcript_exon_variant	5/14	2		ENSP00000390891.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2024

The c.23T>G (p.V8G) alteration is located in exon 2 (coding exon 1) of the MRPL30 gene. This alteration results from a T to G substitution at nucleotide position 23, causing the valine (V) at amino acid position 8 to be replaced by a glycine (G). 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	0.10
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.016	.;T;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.51	T;.;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	.;L;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.90	N;N;N
REVEL	Benign	0.20
Sift	Benign	0.13	T;T;T
Sift4G	Uncertain	0.011	D;D;D
Polyphen		0.099	.;B;.
Vest4		0.37
MutPred		0.45		Loss of stability (P = 0.0031);Loss of stability (P = 0.0031);Loss of stability (P = 0.0031);
MVP		0.47
MPC		0.10
ClinPred		0.20	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.043
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-99802689;