10-73250877-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_016065.4(MRPS16):c.389C>G(p.Thr130Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 1,614,068 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T130A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 22 hom. )

Consequence

MRPS16
NM_016065.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.819

Publications

4 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038076937).

BP6

Variant 10-73250877-G-C is Benign according to our data. Variant chr10-73250877-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 214673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 22 AR gene

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.389C>G	p.Thr130Arg	missense	Exon 3 of 3	NP_057149.1	Q9Y3D3-1
MRPS16	NM_001410935.1		c.274+886C>G		intron	N/A	NP_001397864.1	A6ND22
DNAJC9-AS1	NR_038373.1		n.175+2427G>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRPS16	ENST00000372945.8	TSL:1 MANE Select	c.389C>G	p.Thr130Arg	missense	Exon 3 of 3	ENSP00000362036.3	Q9Y3D3-1
DNAJC9-AS1	ENST00000440197.2	TSL:1	n.182+2427G>C		intron	N/A
MRPS16	ENST00000918450.1		c.191C>G	p.Thr64Arg	missense	Exon 3 of 3	ENSP00000588509.1

Frequencies

GnomAD3 genomes

AF:

0.00329

AC:

500

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00547

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00323

AC:

811

AN:

251434

AF XY:

0.00339

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00130

Gnomad NFE exome

AF:

0.00534

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00431

AC:

6299

AN:

1461758

Hom.:

Cov.:

AF XY:

0.00425

AC XY:

3087

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.000657

AC:

AN:

33478

American (AMR)

AF:

0.00244

AC:

109

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.000153

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00203

AC:

175

AN:

86252

European-Finnish (FIN)

AF:

0.00186

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00105

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00512

AC:

5693

AN:

1111994

Other (OTH)

AF:

0.00316

AC:

191

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

367

734

1100

1467

1834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

218

436

654

872

1090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00328

AC:

500

AN:

152310

Hom.:

Cov.:

AF XY:

0.00317

AC XY:

236

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.000842

AC:

AN:

41576

American (AMR)

AF:

0.00386

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00186

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00179

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00547

AC:

372

AN:

68020

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

102

127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00391

Hom.:

Bravo

AF:

0.00302

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00523

AC:

ExAC

AF:

0.00327

AC:

397

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00491

EpiControl

AF:

0.00456

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

MRPS16-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.0071

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.73

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.31

M_CAP

Benign

0.0055

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

0.82

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.93

REVEL

Benign

0.12

Sift

Benign

0.18

Sift4G

Benign

0.40

Polyphen

0.013

Vest4

0.32

MVP

0.25

MPC

0.27

ClinPred

0.0037

GERP RS

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.11

gMVP

0.46

Mutation Taster

=100/0

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over