8-54136520-C-T

Variant names:

• chr8-54136520-C-T
• rs933569235
• NM_014175.4:c.118C>T

Variant summary

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

The NM_014175.4(MRPL15):​c.118C>T​(p.Pro40Ser) 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. 15/21 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. P40A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MRPL15 NM_014175.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43
• Publications: 0 publications found

Genes affected

MRPL15 (HGNC:14054): (mitochondrial ribosomal protein L15) 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 that belongs to the EcoL15 ribosomal protein family. A pseudogene corresponding to this gene is found on chromosome 15q. [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=0.25429636).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014175.4. 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
	MRPL15	NM_014175.4	MANE Select	c.118C>T	p.Pro40Ser	missense	Exon 2 of 5	NP_054894.1	Q9P015

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL15	ENST00000260102.9	TSL:1 MANE Select	c.118C>T	p.Pro40Ser	missense	Exon 2 of 5	ENSP00000260102.4	Q9P015
	MRPL15	ENST00000867845.1		c.118C>T	p.Pro40Ser	missense	Exon 2 of 6	ENSP00000537904.1
	MRPL15	ENST00000938846.1		c.115C>T	p.Pro39Ser	missense	Exon 2 of 5	ENSP00000608905.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.055
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.4
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.71	N
REVEL	Benign	0.031
Sift	Benign	0.41	T
Sift4G	Benign	0.28	T
Polyphen		0.0080	B
Vest4		0.41
MutPred		0.38		Gain of phosphorylation at P40 (P = 2e-04)
MVP		0.69
MPC		0.28
ClinPred		0.67	D
GERP RS		4.8
PromoterAI		-0.0051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.51
Mutation Taster		=95/5	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: rs933569235; hg19: chr8-55049080;