11-66438667-T-C

Position:

• chr11-66438667-T-C

Variant summary

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

The NM_016050.5(MRPL11):​c.88A>G​(p.Met30Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,413,416 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MRPL11 NM_016050.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.783

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]

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=0.12313622).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL11	NM_016050.5	c.88A>G	p.Met30Val	missense_variant	1/5	ENST00000310999.11	NP_057134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL11	ENST00000310999.11	c.88A>G	p.Met30Val	missense_variant	1/5	1	NM_016050.5	ENSP00000308897	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1413416 Hom.: 0 Cov.: 30 AF XY: 0.00000143 AC XY: 1 AN XY: 699798

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: 0.00000184

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 05, 2022

The c.88A>G (p.M30V) alteration is located in exon 1 (coding exon 1) of the MRPL11 gene. This alteration results from a A to G substitution at nucleotide position 88, causing the methionine (M) at amino acid position 30 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	0.075
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.033	T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.85	T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.025	N;N
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.16	N;N
REVEL	Benign	0.098
Sift	Benign	0.48	T;T
Sift4G	Benign	0.37	T;T
Polyphen		0.0	B;.
Vest4		0.25
MutPred		0.39		Loss of MoRF binding (P = 0.1116);Loss of MoRF binding (P = 0.1116);
MVP		0.42
MPC		0.17
ClinPred		0.27	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs200954914; hg19: chr11-66206138;