rs1953589843

Variant names:

• chr12-93501210-A-G
• rs1953589843
• NM_014050.4:c.418A>G

Variant summary

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

The NM_014050.4(MRPL42):​c.418A>G​(p.Lys140Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MRPL42 NM_014050.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.81
• Publications: 0 publications found

Genes affected

MRPL42 (HGNC:14493): (mitochondrial ribosomal protein L42) 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 protein identified as belonging to both the 28S and the 39S subunits. Alternative splicing results in multiple transcript variants. Pseudogenes corresponding to this gene are found on chromosomes 4q, 6p, 6q, 7p, and 15q. [provided by RefSeq, May 2011]

SOCS2-AS1 (HGNC:27054): (SOCS2 antisense RNA 1)

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=0.2443093).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014050.4. 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
	MRPL42	NM_014050.4	MANE Select	c.418A>G	p.Lys140Glu	missense	Exon 6 of 6	NP_054769.1	Q9Y6G3
	MRPL42	NM_172177.5		c.418A>G	p.Lys140Glu	missense	Exon 6 of 6	NP_751917.1	Q9Y6G3
	MRPL42	NR_038159.2		n.576A>G		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL42	ENST00000549982.6	TSL:1 MANE Select	c.418A>G	p.Lys140Glu	missense	Exon 6 of 6	ENSP00000449884.1	Q9Y6G3
	MRPL42	ENST00000358678.7	TSL:1	n.*367A>G		non_coding_transcript_exon	Exon 7 of 7	ENSP00000351506.3	J3KP21
	MRPL42	ENST00000358678.7	TSL:1	n.*367A>G		3_prime_UTR	Exon 7 of 7	ENSP00000351506.3	J3KP21

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449910 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 720924

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32838

American (AMR) AF: 0.00 AC: 0 AN: 42480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25974

East Asian (EAS) AF: 0.00 AC: 0 AN: 39182

South Asian (SAS) AF: 0.00 AC: 0 AN: 83198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4642

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108486

Other (OTH) AF: 0.00 AC: 0 AN: 59870

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.25
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.8
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.18
Sift	Benign	0.063	T
Sift4G	Benign	0.12	T
Polyphen		0.49	P
Vest4		0.31
MutPred		0.51		Loss of MoRF binding (P = 2e-04)
MVP		0.30
MPC		0.44
ClinPred		0.97	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.13
Mutation Taster		=89/11	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: rs1953589843; hg19: chr12-93894986;