11-59806589-C-T

Variant names:

• chr11-59806589-C-T
• rs758445490
• NM_017840.4:c.514G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017840.4(MRPL16):​c.514G>A​(p.Val172Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: MRPL16 NM_017840.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.13
• Publications: 3 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017840.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL16	NM_017840.4	MANE Select	c.514G>A	p.Val172Met	missense	Exon 4 of 4	NP_060310.1	Q9NX20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL16	ENST00000300151.5	TSL:1 MANE Select	c.514G>A	p.Val172Met	missense	Exon 4 of 4	ENSP00000300151.4	Q9NX20
	MRPL16	ENST00000923617.1		c.535G>A	p.Val179Met	missense	Exon 4 of 4	ENSP00000593676.1
	MRPL16	ENST00000923616.1		c.448G>A	p.Val150Met	missense	Exon 3 of 3	ENSP00000593675.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.1
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.99	D
Vest4		0.66
MVP		0.62
MPC		0.57
ClinPred		0.97	D
GERP RS		6.1
Varity_R		0.65
gMVP		0.84
Mutation Taster		=33/67	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs758445490; hg19: chr11-59574062;