11-59806484-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_017840.4(MRPL16):c.619C>T(p.Arg207Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 1,614,192 control chromosomes in the GnomAD database, including 81 homozygotes. 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R207P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.012 ( 40 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 41 hom. )

Consequence

MRPL16
NM_017840.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.530

Publications

3 publications found

Variant links:

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]

MRPL16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025645494).

BP6

Variant 11-59806484-G-A is Benign according to our data. Variant chr11-59806484-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 445686.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0125 (1903/152302) while in subpopulation AFR AF = 0.0429 (1782/41538). AF 95% confidence interval is 0.0412. There are 40 homozygotes in GnomAd4. There are 909 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 40 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL16	NM_017840.4 link	c.619C>T	p.Arg207Cys	missense_variant	Exon 4 of 4	ENST00000300151.5	NP_060310.1	Q9NX20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL16	ENST00000300151.5 link	c.619C>T	p.Arg207Cys	missense_variant	Exon 4 of 4	1	NM_017840.4	ENSP00000300151.4		Q9NX20
MRPL16	ENST00000534340.1 link	c.*51C>T		downstream_gene_variant		3		ENSP00000436592.1		E9PI14

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1904

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0431

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00451

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00861

GnomAD2 exomes

AF:

0.00330

AC:

831

AN:

251490

AF XY:

0.00252

show subpopulations

Gnomad AFR exome

AF:

0.0426

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00456

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000193

Gnomad OTH exome

AF:

0.00195

GnomAD4 exome

AF:

0.00138

AC:

2013

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

883

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.0465

AC:

1556

AN:

33480

American (AMR)

AF:

0.00195

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00406

AC:

106

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000927

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000881

AC:

AN:

1112010

Other (OTH)

AF:

0.00248

AC:

150

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

133

266

400

533

666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0125

AC:

1903

AN:

152302

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

909

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0429

AC:

1782

AN:

41538

American (AMR)

AF:

0.00451

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68024

Other (OTH)

AF:

0.00852

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

181

271

362

452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0104

Hom.:

Bravo

AF:

0.0142

ESP6500AA

AF:

0.0411

AC:

181

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.00403

AC:

489

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 15, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

0.53

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.10

Sift

Uncertain

0.017

Sift4G

Uncertain

0.030

Polyphen

0.92

Vest4

0.088

MVP

0.42

MPC

0.17

ClinPred

0.026

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.49

Mutation Taster

=81/19

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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11-59806484-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over