Variant 8-120432042-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014078.6(MRPL13):c.233C>T(p.Ser78Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MRPL13
NM_014078.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.46

Variant links:

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]

MRPL13 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3411808).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL13	NM_014078.6 link	c.233C>T	p.Ser78Phe	missense_variant	Exon 3 of 7	ENST00000306185.8	NP_054797.2	Q9BYD1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MRPL13	ENST00000306185.8 link	c.233C>T	p.Ser78Phe	missense_variant	Exon 3 of 7	1	NM_014078.6	ENSP00000306548.3	Q9BYD1
MRPL13	ENST00000518696.5 link	n.152-6676C>T		intron_variant	Intron 2 of 5	1		ENSP00000428867.1	E5RFI2
MRPL13	ENST00000518918.1 link	c.161C>T	p.Ser54Phe	missense_variant	Exon 3 of 6	2		ENSP00000430545.1	E5RJI7
MRPL13	ENST00000520677.1 link	n.157-6676C>T		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000409

AC:

AN:

244250

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132052

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000561

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449404

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721000

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.233C>T (p.S78F) alteration is located in exon 3 (coding exon 3) of the MRPL13 gene. This alteration results from a C to T substitution at nucleotide position 233, causing the serine (S) at amino acid position 78 to be replaced by a phenylalanine (F). 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

Uncertain

0.42

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Pathogenic

0.26

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.10

T;.

Eigen

Benign

0.030

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.0035

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.63

N;.

PrimateAI

Uncertain

0.63

PROVEAN

Benign

1.9

N;N

REVEL

Uncertain

0.42

Sift

Benign

0.97

T;T

Sift4G

Benign

0.70

T;.

Polyphen

0.037

B;.

Vest4

0.85

MutPred

0.53

Loss of disorder (P = 0.0012);.;

MVP

0.47

MPC

0.23

ClinPred

0.42

GERP RS

6.0

Varity_R

0.40

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over