chr11-68896547-G-A

Variant names:

• chr11-68896547-G-A
• rs1857793320
• NM_181514.2:c.364C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181514.2(MRPL21):​c.364C>T​(p.Leu122Phe) 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: MRPL21 NM_181514.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.441
• Publications: 0 publications found

Genes affected

MRPL21 (HGNC:14479): (mitochondrial ribosomal protein L21) 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 different isoforms were identified through sequence analysis although some may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08329958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL21	NM_181514.2	c.364C>T	p.Leu122Phe	missense_variant	Exon 4 of 7	ENST00000362034.7	NP_852615.1
MRPL21	NM_181515.2	c.109C>T	p.Leu37Phe	missense_variant	Exon 4 of 7		NP_852616.1
MRPL21	XM_005273823.5	c.364C>T	p.Leu122Phe	missense_variant	Exon 4 of 6		XP_005273880.1
MRPL21	XR_247190.5	n.386C>T		non_coding_transcript_exon_variant	Exon 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL21	ENST00000362034.7	c.364C>T	p.Leu122Phe	missense_variant	Exon 4 of 7	1	NM_181514.2	ENSP00000354580.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.364C>T (p.L122F) alteration is located in exon 4 (coding exon 4) of the MRPL21 gene. This alteration results from a C to T substitution at nucleotide position 364, causing the leucine (L) at amino acid position 122 to be replaced by a phenylalanine (F). 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	0.19
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.53
DANN	Benign	0.94
DEOGEN2	Benign	0.018	.;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.083	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.77	.;N;.
PhyloP100		0.44
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.080
Sift	Benign	0.049	D;D;T
Sift4G	Benign	0.083	T;T;T
Polyphen		0.60	.;P;.
Vest4		0.24
MutPred		0.40		.;Loss of solvent accessibility (P = 0.0561);.;
MVP		0.15
MPC		0.33
ClinPred		0.14	T
GERP RS		-5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.44
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs1857793320; hg19: chr11-68664015; COSMIC: COSV100751938; COSMIC: COSV100751938;