Variant 11-66438735-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000310999.11(MRPL11):c.20C>T(p.Ala7Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000056 in 1,570,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

MRPL11
ENST00000310999.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42

Variant links:

Genes affected

MRPL11 (HGNC:14042): (mitochondrial ribosomal protein L11) This nuclear gene encodes a 39S subunit component of the mitochondial ribosome. Alternative splicing results in multiple transcript variants. Pseudogenes for this gene are found on chromosomes 5 and 12. [provided by RefSeq, May 2014]

MRPL11 links:

MRPL11 (HGNC:):

MRPL11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.095828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL11	NM_016050.5 linkuse as main transcript	c.20C>T	p.Ala7Val	missense_variant	1/5	ENST00000310999.11	NP_057134.1	Q9Y3B7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL11	ENST00000310999.11 linkuse as main transcript	c.20C>T	p.Ala7Val	missense_variant	1/5	1	NM_016050.5	ENSP00000308897.7		Q9Y3B7-1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000341

AC:

AN:

205032

Hom.:

AF XY:

0.0000524

AC XY:

AN XY:

114552

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.000125

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000543

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000529

AC:

AN:

1418684

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

703600

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000263

Gnomad4 ASJ exome

AF:

0.0000408

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000651

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000792

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.0000167

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.20C>T (p.A7V) alteration is located in exon 1 (coding exon 1) of the MRPL11 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

0.16

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.087

T;.;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.096

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.95

L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.054

Sift

Benign

0.18

T;T;T

Sift4G

Benign

0.14

T;T;D

Polyphen

0.0020

B;B;.

Vest4

0.18

MVP

0.36

MPC

0.17

ClinPred

0.051

GERP RS

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.047

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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