rs994442221

Variant names:

• chr2-74472123-C-A
• rs994442221
• NM_053050.5:c.335G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-74472123-C-A
• chr2-74472123-C-G
• chr2-74472123-C-T

Variant summary

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

The NM_053050.5(MRPL53):​c.335G>T​(p.Arg112Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R112P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRPL53 NM_053050.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490
• Publications: 0 publications found

Genes affected

MRPL53 (HGNC:16684): (mitochondrial ribosomal protein L53) 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. A pseudogene corresponding to this gene is found on chromosome 1p. [provided by RefSeq, Jul 2008]

CCDC142 (HGNC:25889): (coiled-coil domain containing 142)

ENSG00000286883 (HGNC:):

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=0.1510644).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053050.5. 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
	MRPL53	NM_053050.5	MANE Select	c.335G>T	p.Arg112Leu	missense	Exon 3 of 3	NP_444278.1	Q96EL3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL53	ENST00000258105.8	TSL:1 MANE Select	c.335G>T	p.Arg112Leu	missense	Exon 3 of 3	ENSP00000258105.7	Q96EL3
	MRPL53	ENST00000906488.1		c.332G>T	p.Arg111Leu	missense	Exon 3 of 3	ENSP00000576547.1
	MRPL53	ENST00000409710.1	TSL:2	c.*9G>T		3_prime_UTR	Exon 2 of 2	ENSP00000386920.1	B9A051

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.49
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.095
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.089	B
Vest4		0.47
MutPred		0.29		Gain of stability (P = 0.0053)
MVP		0.34
MPC		1.5
ClinPred		0.94	D
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.28
Mutation Taster		=99/1	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: rs994442221; hg19: chr2-74699250;