8-120432106-C-A

Variant names:

• chr8-120432106-C-A
• rs770466745
• NM_014078.6:c.169G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014078.6(MRPL13):​c.169G>T​(p.Val57Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000207 in 1,448,962 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MRPL13 NM_014078.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.75

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.887

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL13	NM_014078.6	c.169G>T	p.Val57Phe	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.169G>T	p.Val57Phe	missense_variant	Exon 3 of 7	1	NM_014078.6	ENSP00000306548.3
MRPL13	ENST00000518696.5	n.152-6740G>T		intron_variant	Intron 2 of 5	1		ENSP00000428867.1
MRPL13	ENST00000518918.1	c.97G>T	p.Val33Phe	missense_variant	Exon 3 of 6	2		ENSP00000430545.1
MRPL13	ENST00000520677.1	n.157-6740G>T		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1448962 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 720402

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.75	D;.
Eigen	Pathogenic	0.99
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.060	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Uncertain	0.53	D
MutationAssessor	Pathogenic	4.2	H;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Pathogenic	0.84
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;.
Polyphen		0.97	D;.
Vest4		0.92
MutPred		0.72		Gain of catalytic residue at V57 (P = 0.2608);.;
MVP		0.75
MPC		0.64
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.93
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs770466745; hg19: chr8-121444346;