5-72223847-C-A

Position:

chr5-72223847-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000261413.10(MRPS27):c.841G>T(p.Asp281Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,938 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D281N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

MRPS27
ENST00000261413.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.551

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:

MRPS27 (HGNC:):

MRPS27 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24124554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS27	NM_015084.3 linkuse as main transcript	c.841G>T	p.Asp281Tyr	missense_variant	10/11	ENST00000261413.10	NP_055899.2	Q92552-1A0A024RAJ1
MRPS27	NM_001286748.2 linkuse as main transcript	c.883G>T	p.Asp295Tyr	missense_variant	11/12		NP_001273677.1	Q92552-2Q6PKB3
MRPS27	NM_001286751.2 linkuse as main transcript	c.673G>T	p.Asp225Tyr	missense_variant	10/11		NP_001273680.1	G5EA06

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS27	ENST00000261413.10 linkuse as main transcript	c.841G>T	p.Asp281Tyr	missense_variant	10/11	1	NM_015084.3	ENSP00000261413.5		Q92552-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

250074

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135166

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460938

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726696

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2023

The c.841G>T (p.D281Y) alteration is located in exon 10 (coding exon 10) of the MRPS27 gene. This alteration results from a G to T substitution at nucleotide position 841, causing the aspartic acid (D) at amino acid position 281 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

T;T;.;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.73

T;T;T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.24

T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.3

M;.;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.3

D;D;D;D

REVEL

Benign

0.091

Sift

Uncertain

0.0090

D;D;D;D

Sift4G

Uncertain

0.0080

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.52

MutPred

0.51

Loss of disorder (P = 0.0205);.;.;.;

MVP

0.42

MPC

0.42

ClinPred

0.87

GERP RS

1.5

Varity_R

0.13

gMVP

0.55

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