5-72226137-G-A

Position:

• chr5-72226137-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_015084.3(MRPS27):​c.757C>T​(p.Pro253Ser) variant causes a missense change. The variant allele was found at a frequency of 0.013 in 1,613,796 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (13 hom., cov: 31)
  • Exomes 𝑓: 0.013 (146 hom.)
• Consequence: MRPS27 NM_015084.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.35

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0079297125).
• BP6: Variant 5-72226137-G-A is Benign according to our data. Variant chr5-72226137-G-A is described in ClinVar as [Benign]. Clinvar id is 2655523.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS27	NM_015084.3	c.757C>T	p.Pro253Ser	missense_variant	9/11	ENST00000261413.10	NP_055899.2
MRPS27	NM_001286748.2	c.799C>T	p.Pro267Ser	missense_variant	10/12		NP_001273677.1
MRPS27	NM_001286751.2	c.589C>T	p.Pro197Ser	missense_variant	9/11		NP_001273680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS27	ENST00000261413.10	c.757C>T	p.Pro253Ser	missense_variant	9/11	1	NM_015084.3	ENSP00000261413	P1

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1590 AN: 152094 Hom.: 13 Cov.: 31

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.00839

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.0281

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.0124

GnomAD3 exomes AF: 0.0110 AC: 2752 AN: 250958 Hom.: 28 AF XY: 0.0114 AC XY: 1540 AN XY: 135610

Gnomad AFR exome AF: 0.00222

Gnomad AMR exome AF: 0.00637

Gnomad ASJ exome AF: 0.0140

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00670

Gnomad FIN exome AF: 0.0277

Gnomad NFE exome AF: 0.0131

Gnomad OTH exome AF: 0.00963

GnomAD4 exome AF: 0.0133 AC: 19463 AN: 1461584 Hom.: 146 Cov.: 31 AF XY: 0.0132 AC XY: 9596 AN XY: 727088

Gnomad4 AFR exome AF: 0.00149

Gnomad4 AMR exome AF: 0.00709

Gnomad4 ASJ exome AF: 0.0150

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00736

Gnomad4 FIN exome AF: 0.0267

Gnomad4 NFE exome AF: 0.0143

Gnomad4 OTH exome AF: 0.0117

GnomAD4 genome AF: 0.0105 AC: 1591 AN: 152212 Hom.: 13 Cov.: 31 AF XY: 0.0108 AC XY: 801 AN XY: 74406

Gnomad4 AFR AF: 0.00217

Gnomad4 AMR AF: 0.00838

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.0281

Gnomad4 NFE AF: 0.0138

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0129 Hom.: 27

Bravo AF: 0.00908

TwinsUK AF: 0.0127 AC: 47

ALSPAC AF: 0.0138 AC: 53

ESP6500AA AF: 0.00272 AC: 12

ESP6500EA AF: 0.0148 AC: 127

ExAC AF: 0.0104 AC: 1263

Asia WGS AF: 0.00202 AC: 8 AN: 3478

EpiCase AF: 0.0142

EpiControl AF: 0.0139

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2023

MRPS27: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T;T;.;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D;D;D;D
MetaRNN	Benign	0.0079	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.18	T;T;T;T
Sift4G	Benign	0.25	T;T;T;T
Polyphen		1.0	D;.;.;.
Vest4		0.34
MPC		0.41
ClinPred		0.019	T
GERP RS		4.9
Varity_R		0.061
gMVP		0.33

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

Other links and lift over

dbSNP: rs114360965; hg19: chr5-71521964;