rs17376173

chr5-72261486-A-Gchr5-72261486-A-T

Variant summary

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

The NM_015084.3(MRPS27):c.282-23358T>C 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 151,442 control chromosomes in the GnomAD database, including 5,210 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 (5210 hom., cov: 31)
• Consequence: MRPS27 NM_015084.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180

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 -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	UniProt
MRPS27	NM_015084.3	c.282-23358T>C		intron_variant		ENST00000261413.10
MRPS27	NM_001286748.2	c.282-19798T>C		intron_variant
MRPS27	NM_001286751.2	c.114-23358T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPS27	ENST00000261413.10	c.282-23358T>C		intron_variant		1	NM_015084.3	P1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35106 AN: 151324 Hom.: 5209 Cov.: 31

Gnomad AFR AF: 0.0690

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0238

Gnomad SAS AF: 0.280

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: 35101 AN: 151442 Hom.: 5210 Cov.: 31 AF XY: 0.232 AC XY: 17169 AN XY: 73996

Gnomad4 AFR AF: 0.0688

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.0238

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.214

Alfa AF: 0.204 Hom.: 637

Bravo AF: 0.209

Asia WGS AF: 0.151 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.99
Dann	Benign	0.82

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: rs17376173; hg19: chr5-71557313;