Variant 5-72223817-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015084.3(MRPS27):c.871A>G(p.Thr291Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000626 in 1,613,882 control chromosomes in the GnomAD database, including 5 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 0.0033 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00035 ( 2 hom. )

Consequence

MRPS27
NM_015084.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.40

Variant links:

Genes affected

MRPS27 (HGNC:14512): (mitochondrial ribosomal protein S27) 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 may be a functional partner of the death associated protein 3 (DAP3). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2013]

MRPS27 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0068886876).

BP6

Variant 5-72223817-T-C is Benign according to our data. Variant chr5-72223817-T-C is described in ClinVar as [Benign]. Clinvar id is 787821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MRPS27	NM_015084.3 linkuse as main transcript	c.871A>G	p.Thr291Ala	missense_variant	10/11	ENST00000261413.10	NP_055899.2
MRPS27	NM_001286748.2 linkuse as main transcript	c.913A>G	p.Thr305Ala	missense_variant	11/12		NP_001273677.1
MRPS27	NM_001286751.2 linkuse as main transcript	c.703A>G	p.Thr235Ala	missense_variant	10/11		NP_001273680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS27	ENST00000261413.10 linkuse as main transcript	c.871A>G	p.Thr291Ala	missense_variant	10/11	1	NM_015084.3	ENSP00000261413	P1	Q92552-1

Frequencies

GnomAD3 genomes

AF:

0.00332

AC:

505

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0117

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000918

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000961

AC:

241

AN:

250846

Hom.:

AF XY:

0.000598

AC XY:

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.0129

Gnomad AMR exome

AF:

0.000810

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000346

AC:

506

AN:

1461704

Hom.:

Cov.:

AF XY:

0.000289

AC XY:

210

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.0125

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.000778

GnomAD4 genome

AF:

0.00332

AC:

505

AN:

152178

Hom.:

Cov.:

AF XY:

0.00296

AC XY:

220

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0117

Gnomad4 AMR

AF:

0.000917

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000620

Hom.:

Bravo

AF:

0.00403

ESP6500AA

AF:

0.0143

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00119

AC:

145

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	Labcorp Genetics (formerly Invitae), Labcorp	May 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0022

T;T;.;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.35

T;T;T;T

MetaRNN

Benign

0.0069

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.53

N;N;N;N

REVEL

Benign

0.043

Sift

Benign

0.33

T;T;T;T

Sift4G

Benign

0.58

T;T;T;T

Polyphen

0.0070

B;.;.;.

Vest4

0.040

MVP

0.38

MPC

0.072

ClinPred

0.0050

GERP RS

3.6

Varity_R

0.029

gMVP

0.093

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