NM_021134.4:c.211C>T

Variant names:

• chr11-1952197-C-T
• rs1223735915
• NM_021134.4:c.211C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_021134.4(MRPL23):​c.211C>T​(p.Arg71Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R71Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 1)
  • Exomes 𝑓: 0.000013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MRPL23 NM_021134.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74
• Publications: 0 publications found

Genes affected

MRPL23 (HGNC:10322): (mitochondrial ribosomal protein L23) 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. The gene is biallelically expressed, despite its location within a region of imprinted genes on chromosome 11. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.798

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021134.4. 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
	MRPL23	NM_021134.4	MANE Select	c.211C>T	p.Arg71Trp	missense	Exon 3 of 5	NP_066957.3
	MRPL23	NM_001400176.1		c.211C>T	p.Arg71Trp	missense	Exon 3 of 7	NP_001387105.1
	MRPL23	NM_001400179.1		c.211C>T	p.Arg71Trp	missense	Exon 3 of 6	NP_001387108.1	A8MYK1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL23	ENST00000397298.8	TSL:1 MANE Select	c.211C>T	p.Arg71Trp	missense	Exon 3 of 5	ENSP00000380466.3	Q16540
	MRPL23	ENST00000924183.1		c.211C>T	p.Arg71Trp	missense	Exon 3 of 5	ENSP00000594242.1
	MRPL23	ENST00000397297.7	TSL:2	c.211C>T	p.Arg71Trp	missense	Exon 3 of 6	ENSP00000380465.3	A8MYK1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 7680 Hom.: 0 Cov.: 1

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250756 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000132 AC: 2 AN: 151550 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 79670

African (AFR) AF: 0.00 AC: 0 AN: 2540

American (AMR) AF: 0.00 AC: 0 AN: 4974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4590

East Asian (EAS) AF: 0.00 AC: 0 AN: 5794

South Asian (SAS) AF: 0.00 AC: 0 AN: 13590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 638

European-Non Finnish (NFE) AF: 0.0000198 AC: 2 AN: 100832

Other (OTH) AF: 0.00 AC: 0 AN: 8680

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 7680 Hom.: 0 Cov.: 1 AF XY: 0.00 AC XY: 0 AN XY: 3160

African (AFR) AF: 0.00 AC: 0 AN: 614

American (AMR) AF: 0.00 AC: 0 AN: 444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 246

East Asian (EAS) AF: 0.00 AC: 0 AN: 120

South Asian (SAS) AF: 0.00 AC: 0 AN: 74

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 26

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 5572

Other (OTH) AF: 0.00 AC: 0 AN: 94

Alfa AF: 0.00 Hom.: 0

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	Uncertain	0.50
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	-0.0017
FATHMM_MKL	Benign	0.68	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.069	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		1.7
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.45		Loss of disorder (P = 0.0183)
MVP		0.61
MPC		0.70
ClinPred		0.97	D
GERP RS		1.7
Varity_R		0.90
gMVP		0.68
Mutation Taster		=50/50

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: rs1223735915; hg19: chr11-1973427;