5-72232283-T-C

Position:

• chr5-72232283-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015084.3(MRPS27):​c.591+160A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,122 control chromosomes in the GnomAD database, including 5,238 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (5238 hom., cov: 33)
• Consequence: MRPS27 NM_015084.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS27	NM_015084.3	c.591+160A>G		intron_variant		ENST00000261413.10	NP_055899.2
MRPS27	NM_001286748.2	c.633+160A>G		intron_variant			NP_001273677.1
MRPS27	NM_001286751.2	c.423+160A>G		intron_variant			NP_001273680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS27	ENST00000261413.10	c.591+160A>G		intron_variant		1	NM_015084.3	ENSP00000261413.5

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35330 AN: 152004 Hom.: 5237 Cov.: 33

Gnomad AFR AF: 0.0713

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0236

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.217

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.232 AC: 35326 AN: 152122 Hom.: 5238 Cov.: 33 AF XY: 0.232 AC XY: 17288 AN XY: 74360

Gnomad4 AFR AF: 0.0710

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.0236

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.214

Alfa AF: 0.289 Hom.: 3705

Bravo AF: 0.209

Asia WGS AF: 0.152 AC: 526 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.84
DANN	Benign	0.56

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: rs3213894; hg19: chr5-71528110;