1-228106801-C-A

Variant names:

• chr1-228106801-C-A
• NM_181463.3:c.346G>T

Variant summary

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

The NM_181463.3(MRPL55):​c.346G>T​(p.Val116Leu) 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. 15/21 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: MRPL55 NM_181463.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.75

Genes affected

MRPL55 (HGNC:16686): (mitochondrial ribosomal protein L55) 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. Multiple transcript variants encoding two different isoforms were identified through sequence analysis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06493223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL55	NM_181463.3	c.346G>T	p.Val116Leu	missense_variant	Exon 5 of 5	ENST00000336520.8	NP_852128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL55	ENST00000336520.8	c.346G>T	p.Val116Leu	missense_variant	Exon 5 of 5	2	NM_181463.3	ENSP00000337342.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.454G>T (p.V152L) alteration is located in exon 6 (coding exon 4) of the MRPL55 gene. This alteration results from a G to T substitution at nucleotide position 454, causing the valine (V) at amino acid position 152 to be replaced by a leucine (L). 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	0.088
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.021
DANN	Benign	0.76
DEOGEN2	Benign	0.021	T;T;T;T;T;T;.;T;T;T;T;T;T;T;T;T;T;T;T;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.33	.;T;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.065	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	.;.;L;L;L;L;.;L;L;L;L;L;L;L;L;.;L;L;L;L;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	.;.;N;N;N;N;N;N;N;N;N;N;N;N;N;.;N;N;N;N;N
REVEL	Benign	0.018
Sift	Benign	0.40	.;.;T;T;T;T;T;T;T;T;T;T;T;T;T;.;T;T;T;T;T
Sift4G	Benign	0.20	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.026, 0.055	.;.;B;B;B;B;B;B;B;B;B;B;B;B;B;.;B;B;B;B;B
Vest4		0.16
MutPred		0.54		.;.;Loss of MoRF binding (P = 0.1057);Loss of MoRF binding (P = 0.1057);Loss of MoRF binding (P = 0.1057);Loss of MoRF binding (P = 0.1057);.;Loss of MoRF binding (P = 0.1057);Loss of MoRF binding (P = 0.1057);Loss of MoRF binding (P = 0.1057);Loss of MoRF binding (P = 0.1057);Loss of MoRF binding (P = 0.1057);Loss of MoRF binding (P = 0.1057);Loss of MoRF binding (P = 0.1057);Loss of MoRF binding (P = 0.1057);.;Loss of MoRF binding (P = 0.1057);Loss of MoRF binding (P = 0.1057);Loss of MoRF binding (P = 0.1057);Loss of MoRF binding (P = 0.1057);.;
MVP		0.040
MPC		0.30
ClinPred		0.050	T
GERP RS		-3.0
Varity_R		0.024
gMVP		0.12

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: chr1-228294502;