NM_181514.2:c.368C>G

Variant names:

• chr11-68896543-G-C
• NM_181514.2:c.368C>G

Variant summary

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

The NM_181514.2(MRPL21):​c.368C>G​(p.Ala123Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MRPL21 NM_181514.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

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

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=0.10709682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL21	NM_181514.2	c.368C>G	p.Ala123Gly	missense_variant	Exon 4 of 7	ENST00000362034.7	NP_852615.1
MRPL21	NM_181515.2	c.113C>G	p.Ala38Gly	missense_variant	Exon 4 of 7		NP_852616.1
MRPL21	XM_005273823.5	c.368C>G	p.Ala123Gly	missense_variant	Exon 4 of 6		XP_005273880.1
MRPL21	XR_247190.5	n.390C>G		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.368C>G	p.Ala123Gly	missense_variant	Exon 4 of 7	1	NM_181514.2	ENSP00000354580.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	10
DANN	Benign	0.70
DEOGEN2	Benign	0.015	.;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.60	T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.94	.;L;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.58	N;N;N
REVEL	Benign	0.067
Sift	Benign	0.21	T;T;T
Sift4G	Benign	0.11	T;T;T
Polyphen		0.0030	.;B;.
Vest4		0.19
MutPred		0.34		.;Loss of stability (P = 0.0777);.;
MVP		0.17
MPC		0.17
ClinPred		0.25	T
GERP RS		-3.5
Varity_R		0.083
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr11-68664011;