Genetic Variant NM_016065.4:c.347G>C (chr10-73250919-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016065.4(MRPS16):c.347G>C(p.Arg116Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. R116L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

MRPS16
NM_016065.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.851

Publications

0 publications found

Variant links:

Genes affected

MRPS16 (HGNC:14048): (mitochondrial ribosomal protein S16) 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 28S subunit protein that belongs to the ribosomal protein S16P family. The encoded protein is one of the most highly conserved ribosomal proteins between mammalian and yeast mitochondria. Three pseudogenes (located at 8q21.3, 20q13.32, 22q12-q13.1) for this gene have been described. [provided by RefSeq, Jul 2008]

MRPS16 links:

DNAJC9-AS1 (HGNC:31432): (DNAJC9 and MRPS16 antisense RNA 1)

DNAJC9-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052408785).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016065.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRPS16	NM_016065.4	MANE Select	c.347G>C	p.Arg116Pro	missense	Exon 3 of 3	NP_057149.1	Q9Y3D3-1
MRPS16	NM_001410935.1		c.274+844G>C		intron	N/A	NP_001397864.1	A6ND22
DNAJC9-AS1	NR_038373.1		n.175+2469C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRPS16	ENST00000372945.8	TSL:1 MANE Select	c.347G>C	p.Arg116Pro	missense	Exon 3 of 3	ENSP00000362036.3	Q9Y3D3-1
DNAJC9-AS1	ENST00000440197.2	TSL:1	n.182+2469C>G		intron	N/A
MRPS16	ENST00000918450.1		c.149G>C	p.Arg50Pro	missense	Exon 3 of 3	ENSP00000588509.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

9.0

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.0073

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.37

M_CAP

Benign

0.014

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.96

MutationAssessor

Benign

2.0

PhyloP100

-0.85

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.2

REVEL

Benign

0.031

Sift

Benign

0.17

Sift4G

Benign

0.23

Polyphen

0.12

Vest4

0.24

MutPred

0.39

Loss of MoRF binding (P = 0.0046)

MVP

0.19

MPC

0.34

ClinPred

0.12

GERP RS

-3.1

Varity_R

0.32

gMVP

0.80

Mutation Taster

=72/28

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over