rs758445490

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-59806589-C-A
• chr11-59806589-C-G
• chr11-59806589-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_017840.4(MRPL16):​c.514G>T​(p.Val172Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V172M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRPL16 NM_017840.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.853

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL16	NM_017840.4	c.514G>T	p.Val172Leu	missense_variant	Exon 4 of 4	ENST00000300151.5	NP_060310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL16	ENST00000300151.5	c.514G>T	p.Val172Leu	missense_variant	Exon 4 of 4	1	NM_017840.4	ENSP00000300151.4
MRPL16	ENST00000534340.1	c.205G>T	p.Val69Leu	missense_variant	Exon 4 of 4	3		ENSP00000436592.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.3	M;.
PhyloP100		6.1
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.037	D;.
Polyphen		0.69	P;.
Vest4		0.68
MutPred		0.77		Gain of helix (P = 0.1736);.;
MVP		0.51
MPC		0.24
ClinPred		0.97	D
GERP RS		6.1
Varity_R		0.75
gMVP		0.86
Mutation Taster		=24/76	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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;