11-59807830-T-A

Position:

• chr11-59807830-T-A

Variant summary

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

The NM_017840.4(MRPL16):​c.141A>T​(p.Lys47Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,456,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.000010 (0 hom.)
• Consequence: MRPL16 NM_017840.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0650

Genes affected

MRPL16 (HGNC:14476): (mitochondrial ribosomal protein L16) 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=0.13646764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL16	NM_017840.4	c.141A>T	p.Lys47Asn	missense_variant	3/4	ENST00000300151.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL16	ENST00000300151.5	c.141A>T	p.Lys47Asn	missense_variant	3/4	1	NM_017840.4	P1
MRPL16	ENST00000534340.1	c.-169A>T		5_prime_UTR_variant	3/4	3
MRPL16	ENST00000525470.1	n.328A>T		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1456420 Hom.: 0 Cov.: 30 AF XY: 0.00000967 AC XY: 7 AN XY: 724234

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: 0.0000117

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome Cov.: 32

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 28, 2022

The c.141A>T (p.K47N) alteration is located in exon 3 (coding exon 3) of the MRPL16 gene. This alteration results from a A to T substitution at nucleotide position 141, causing the lysine (K) at amino acid position 47 to be replaced by an asparagine (N). 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	0.49
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.44	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	0.74	D
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.077
Sift	Benign	0.070	T
Sift4G	Benign	0.22	T
Polyphen		0.79	P
Vest4		0.23
MutPred		0.56		Loss of methylation at K47 (P = 0.0056);
MVP		0.38
MPC		0.25
ClinPred		0.62	D
GERP RS		-0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.75

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: rs1050951899; hg19: chr11-59575303;