rs491671

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

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

GnomAD3 exomes

AF:

0.00330

AC:

831

AN:

251490

Hom.:

AF XY:

0.00252

AC XY:

342

AN XY:

135920

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 SAS exome

AF:

0.0000653

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

Gnomad4 AFR exome

AF:

0.0465

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.00406

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000881

Gnomad4 OTH exome

AF:

0.00248

GnomAD4 genome

AF:

0.0125

AC:

1903

AN:

152302

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

909

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0429

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.00741

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over