NM_015084.3:c.282-19985T>C

Variant names:

• chr5-72258113-A-G
• rs17310329
• NM_015084.3:c.282-19985T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015084.3(MRPS27):​c.282-19985T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 150,082 control chromosomes in the GnomAD database, including 5,091 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 (5091 hom., cov: 28)
• Consequence: MRPS27 NM_015084.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015084.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS27	NM_015084.3	MANE Select	c.282-19985T>C		intron	N/A	NP_055899.2
	MRPS27	NM_001286748.2		c.282-16425T>C		intron	N/A	NP_001273677.1
	MRPS27	NM_001286751.2		c.114-19985T>C		intron	N/A	NP_001273680.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS27	ENST00000261413.10	TSL:1 MANE Select	c.282-19985T>C		intron	N/A	ENSP00000261413.5
	MRPS27	ENST00000515404.5	TSL:1	n.268-19985T>C		intron	N/A
	MRPS27	ENST00000695404.1		c.282-19985T>C		intron	N/A	ENSP00000511886.1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34501 AN: 149982 Hom.: 5090 Cov.: 28

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.0238

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.186

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.230 AC: 34496 AN: 150082 Hom.: 5091 Cov.: 28 AF XY: 0.228 AC XY: 16651 AN XY: 72988

African (AFR) AF: 0.0700 AC: 2876 AN: 41086

American (AMR) AF: 0.187 AC: 2791 AN: 14942

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 787 AN: 3456

East Asian (EAS) AF: 0.0239 AC: 123 AN: 5154

South Asian (SAS) AF: 0.279 AC: 1333 AN: 4782

European-Finnish (FIN) AF: 0.325 AC: 3158 AN: 9716

Middle Eastern (MID) AF: 0.190 AC: 55 AN: 290

European-Non Finnish (NFE) AF: 0.334 AC: 22612 AN: 67662

Other (OTH) AF: 0.210 AC: 438 AN: 2082

Alfa AF: 0.277 Hom.: 1065

Bravo AF: 0.210

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.60
DANN	Benign	0.36
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17310329; hg19: chr5-71553940;