NM_181514.2:c.101C>T

Variant names:

• chr11-68900593-G-A
• NM_181514.2:c.101C>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.101C>T​(p.Ser34Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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: 5.23
• 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=0.23131078).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181514.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL21	NM_181514.2	MANE Select	c.101C>T	p.Ser34Phe	missense	Exon 2 of 7	NP_852615.1	Q7Z2W9-1
	MRPL21	NM_181515.2		c.-168C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	NP_852616.1	Q7Z2W9-2
	MRPL21	NM_181515.2		c.-168C>T		5_prime_UTR	Exon 2 of 7	NP_852616.1	Q7Z2W9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL21	ENST00000362034.7	TSL:1 MANE Select	c.101C>T	p.Ser34Phe	missense	Exon 2 of 7	ENSP00000354580.2	Q7Z2W9-1
	MRPL21	ENST00000567045.5	TSL:2	c.-168C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000457859.1	H3BUY0
	MRPL21	ENST00000450904.6	TSL:2	c.-168C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	ENSP00000389400.2	Q7Z2W9-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.2
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.14
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.038	D
Polyphen		0.031	B
Vest4		0.49
MutPred		0.30		Loss of disorder (P = 0.0067)
MVP		0.29
MPC		0.61
ClinPred		0.92	D
GERP RS		3.0
Varity_R		0.11
gMVP		0.56
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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

hg19: chr11-68668061;