8-120432099-A-T

Variant names:

• chr8-120432099-A-T
• rs774860506
• NM_014078.6:c.176T>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_014078.6(MRPL13):​c.176T>A​(p.Ile59Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRPL13 NM_014078.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.82

Genes affected

MRPL13 (HGNC:14278): (mitochondrial ribosomal protein L13) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.94

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL13	NM_014078.6	c.176T>A	p.Ile59Lys	missense_variant	Exon 3 of 7	ENST00000306185.8	NP_054797.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL13	ENST00000306185.8	c.176T>A	p.Ile59Lys	missense_variant	Exon 3 of 7	1	NM_014078.6	ENSP00000306548.3
MRPL13	ENST00000518696.5	n.152-6733T>A		intron_variant	Intron 2 of 5	1		ENSP00000428867.1
MRPL13	ENST00000518918.1	c.104T>A	p.Ile35Lys	missense_variant	Exon 3 of 6	2		ENSP00000430545.1
MRPL13	ENST00000520677.1	n.157-6733T>A		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	29
DANN	Benign	0.96
DEOGEN2	Uncertain	0.75	D;.
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.052	D
MetaRNN	Pathogenic	0.94	D;D
MetaSVM	Uncertain	-0.011	T
MutationAssessor	Pathogenic	3.5	H;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0010	D;.
Polyphen		0.97	D;.
Vest4		0.87
MutPred		0.79		Gain of MoRF binding (P = 0.0131);.;
MVP		0.70
MPC		0.75
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.87
gMVP		0.94

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

Publications

LitVar

Other links and lift over

dbSNP: rs774860506; hg19: chr8-121444339;