15-88475238-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_022839.5(MRPS11):c.410C>T(p.Ala137Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

MRPS11
NM_022839.5 missense, splice_region

Scores

Splicing: ADA: 0.00009996

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.320

Variant links:

Genes affected

MRPS11 (HGNC:14050): (mitochondrial ribosomal protein S11) 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 28S subunit protein that contains a high level of sequence similarity with ribosomal protein S11P family members. A pseudogene corresponding to this gene is found on chromosome 20. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2016]

MRPS11 links:

ENSG00000173867 (HGNC:):

ENSG00000173867 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04032314).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS11	NM_022839.5 link	c.410C>T	p.Ala137Val	missense_variant, splice_region_variant	Exon 4 of 6	ENST00000325844.9	NP_073750.2	P82912-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS11	ENST00000325844.9 link	c.410C>T	p.Ala137Val	missense_variant, splice_region_variant	Exon 4 of 6	1	NM_022839.5	ENSP00000317376.4		P82912-1
ENSG00000173867	ENST00000649547.1 link	c.*756-9465G>A		intron_variant	Intron 7 of 9			ENSP00000497509.1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000995

AC:

AN:

251278

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000424

AC:

AN:

1461726

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.000429

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.410C>T (p.A137V) alteration is located in exon 4 (coding exon 4) of the MRPS11 gene. This alteration results from a C to T substitution at nucleotide position 410, causing the alanine (A) at amino acid position 137 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

0.10

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.036

T;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.040

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.047

Sift

Benign

0.23

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.30

B;B

Vest4

0.26

MutPred

0.40

Loss of disorder (P = 0.0714);.;

MVP

0.38

MPC

0.23

ClinPred

0.029

GERP RS

-0.010

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.022

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.068

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

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