11-1950912-C-T

Variant names:

• chr11-1950912-C-T
• rs375605257
• NM_021134.4:c.31C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001400172.1(MRPL23):​c.-105C>T variant causes a 5 prime UTR premature start codon gain change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (1 hom., cov: 5)
  • Exomes 𝑓: 0.00029 (15 hom.)
  • Failed GnomAD Quality Control
• Consequence: MRPL23 NM_001400172.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.27
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019785672).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001400172.1. 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.31C>T	p.Arg11Trp	missense	Exon 2 of 5	NP_066957.3
	MRPL23	NM_001400172.1		c.-105C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	NP_001387101.1
	MRPL23	NM_001400176.1		c.31C>T	p.Arg11Trp	missense	Exon 2 of 7	NP_001387105.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL23	ENST00000397298.8	TSL:1 MANE Select	c.31C>T	p.Arg11Trp	missense	Exon 2 of 5	ENSP00000380466.3	Q16540
	MRPL23	ENST00000924183.1		c.31C>T	p.Arg11Trp	missense	Exon 2 of 5	ENSP00000594242.1
	MRPL23	ENST00000397297.7	TSL:2	c.31C>T	p.Arg11Trp	missense	Exon 2 of 6	ENSP00000380465.3	A8MYK1

Frequencies

GnomAD3 genomes AF: 0.000192 AC: 6 AN: 31280 Hom.: 1 Cov.: 5

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.0116

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: 0.000136 AC: 34 AN: 250874 AF XY: 0.000125

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00238

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000707

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000288 AC: 54 AN: 187244 Hom.: 15 Cov.: 0 AF XY: 0.000310 AC XY: 30 AN XY: 96892

African (AFR) AF: 0.000476 AC: 3 AN: 6298

American (AMR) AF: 0.00 AC: 0 AN: 4766

Ashkenazi Jewish (ASJ) AF: 0.00666 AC: 33 AN: 4952

East Asian (EAS) AF: 0.00 AC: 0 AN: 13758

South Asian (SAS) AF: 0.00 AC: 0 AN: 14746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 776

European-Non Finnish (NFE) AF: 0.000102 AC: 12 AN: 117524

Other (OTH) AF: 0.000547 AC: 6 AN: 10962

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000192 AC: 6 AN: 31280 Hom.: 1 Cov.: 5 AF XY: 0.000143 AC XY: 2 AN XY: 13996

African (AFR) AF: 0.00 AC: 0 AN: 10298

American (AMR) AF: 0.00 AC: 0 AN: 1730

Ashkenazi Jewish (ASJ) AF: 0.0116 AC: 6 AN: 518

East Asian (EAS) AF: 0.00 AC: 0 AN: 1168

South Asian (SAS) AF: 0.00 AC: 0 AN: 458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 70

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 14278

Other (OTH) AF: 0.00 AC: 0 AN: 366

Alfa AF: 0.000230 Hom.: 0

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000906 AC: 11

EpiCase AF: 0.000218

EpiControl AF: 0.00

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	0.20
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		6.3
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.20
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.017	D
Polyphen		0.99	D
Vest4		0.29
MVP		0.39
MPC		0.36
ClinPred		0.35	T
GERP RS		4.5
Varity_R		0.72
gMVP		0.50
Mutation Taster		=49/51	disease causing

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: rs375605257; hg19: chr11-1972142; COSMIC: COSV106112738; COSMIC: COSV106112738;