8-120445075-G-A

Variant names:

• chr8-120445075-G-A
• NM_014078.6:c.20C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014078.6(MRPL13):​c.20C>T​(p.Ala7Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MRPL13 NM_014078.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.16

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13322109).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL13	NM_014078.6	c.20C>T	p.Ala7Val	missense_variant	Exon 1 of 7	ENST00000306185.8	NP_054797.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL13	ENST00000306185.8	c.20C>T	p.Ala7Val	missense_variant	Exon 1 of 7	1	NM_014078.6	ENSP00000306548.3
MRPL13	ENST00000518696.5	n.20C>T		non_coding_transcript_exon_variant	Exon 1 of 6	1		ENSP00000428867.1
MRPL13	ENST00000518918.1	c.-173C>T		5_prime_UTR_variant	Exon 1 of 6	2		ENSP00000430545.1
MRPL13	ENST00000520677.1	n.25C>T		non_coding_transcript_exon_variant	Exon 1 of 4	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.20C>T (p.A7V) alteration is located in exon 1 (coding exon 1) of the MRPL13 gene. This alteration results from a C to T substitution at nucleotide position 20, causing the alanine (A) at amino acid position 7 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.028
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.42	N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.22
Sift	Benign	0.34	T
Sift4G	Benign	0.78	T
Polyphen		0.42	B
Vest4		0.12
MutPred		0.33		Loss of glycosylation at P8 (P = 0.1149);
MVP		0.59
MPC		0.13
ClinPred		0.82	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-121457315;