12-27714794-G-A

Position:

chr12-27714794-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021821.4(MRPS35):c.127G>A(p.Gly43Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,598,372 control chromosomes in the GnomAD database, including 19,797 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1372 hom., cov: 32)

Exomes 𝑓: 0.15 ( 18425 hom. )

Consequence

MRPS35
NM_021821.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.17

Variant links:

Genes affected

MRPS35 (HGNC:16635): (mitochondrial ribosomal protein S35) 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 has had confusing nomenclature in the literature. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. Pseudogenes corresponding to this gene are found on chromosomes 3p, 5q, and 10q. [provided by RefSeq, Jul 2010]

MRPS35 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013286173).

BP6

Variant 12-27714794-G-A is Benign according to our data. Variant chr12-27714794-G-A is described in ClinVar as [Benign]. Clinvar id is 1249307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS35	NM_021821.4 linkuse as main transcript	c.127G>A	p.Gly43Arg	missense_variant	2/8	ENST00000081029.8	NP_068593.2	P82673-1
MRPS35	NM_001190864.2 linkuse as main transcript	c.127G>A	p.Gly43Arg	missense_variant	2/7		NP_001177793.1	P82673-2
MRPS35	XM_017019780.2 linkuse as main transcript	c.127G>A	p.Gly43Arg	missense_variant	2/6		XP_016875269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS35	ENST00000081029.8 linkuse as main transcript	c.127G>A	p.Gly43Arg	missense_variant	2/8	1	NM_021821.4	ENSP00000081029.3		P82673-1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18275

AN:

151838

Hom.:

1374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0297

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.135

GnomAD3 exomes

AF:

0.137

AC:

34301

AN:

249872

Hom.:

2540

AF XY:

0.141

AC XY:

19103

AN XY:

135086

show subpopulations

Gnomad AFR exome

AF:

0.0269

Gnomad AMR exome

AF:

0.0836

Gnomad ASJ exome

AF:

0.151

Gnomad EAS exome

AF:

0.171

Gnomad SAS exome

AF:

0.139

Gnomad FIN exome

AF:

0.149

Gnomad NFE exome

AF:

0.160

Gnomad OTH exome

AF:

0.134

GnomAD4 exome

AF:

0.154

AC:

222661

AN:

1446416

Hom.:

18425

Cov.:

AF XY:

0.155

AC XY:

111308

AN XY:

720172

show subpopulations

Gnomad4 AFR exome

AF:

0.0241

Gnomad4 AMR exome

AF:

0.0850

Gnomad4 ASJ exome

AF:

0.154

Gnomad4 EAS exome

AF:

0.165

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.148

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.144

GnomAD4 genome

AF:

0.120

AC:

18272

AN:

151956

Hom.:

1372

Cov.:

AF XY:

0.119

AC XY:

8805

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.0296

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.162

Gnomad4 EAS

AF:

0.181

Gnomad4 SAS

AF:

0.144

Gnomad4 FIN

AF:

0.146

Gnomad4 NFE

AF:

0.166

Gnomad4 OTH

AF:

0.135

Alfa

AF:

0.155

Hom.:

3257

Bravo

AF:

0.110

TwinsUK

AF:

0.173

AC:

640

ALSPAC

AF:

0.167

AC:

643

ESP6500AA

AF:

0.0336

AC:

148

ESP6500EA

AF:

0.160

AC:

1372

ExAC

AF:

0.138

AC:

16785

Asia WGS

AF:

0.163

AC:

566

AN:

3478

EpiCase

AF:

0.159

EpiControl

AF:

0.158

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 13, 2018	This variant is associated with the following publications: (PMID: 29632382) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

6.3

DANN

Benign

0.75

DEOGEN2

Benign

0.0031

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00055

LIST_S2

Benign

0.44

T;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.0

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

1.5

N;N

REVEL

Benign

0.077

Sift

Benign

0.62

T;T

Sift4G

Benign

0.62

T;T

Polyphen

0.0

B;B

Vest4

0.036

MutPred

0.18

Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);

MPC

0.068

ClinPred

0.0019

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.019

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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