5-72232283-T-C

Variant names:

• chr5-72232283-T-C
• rs3213894
• NM_015084.3:c.591+160A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.83).
• 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 rank	MANE	Protein	UniProt
MRPS27	NM_015084.3	c.591+160A>G		intron_variant	Intron 7 of 10	ENST00000261413.10	NP_055899.2
MRPS27	NM_001286748.2	c.633+160A>G		intron_variant	Intron 8 of 11		NP_001273677.1
MRPS27	NM_001286751.2	c.423+160A>G		intron_variant	Intron 7 of 10		NP_001273680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS27	ENST00000261413.10	c.591+160A>G		intron_variant	Intron 7 of 10	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

African (AFR) AF: 0.0710 AC: 2951 AN: 41538

American (AMR) AF: 0.192 AC: 2936 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3468

East Asian (EAS) AF: 0.0236 AC: 122 AN: 5168

South Asian (SAS) AF: 0.280 AC: 1353 AN: 4824

European-Finnish (FIN) AF: 0.344 AC: 3633 AN: 10574

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22712 AN: 67960

Other (OTH) AF: 0.214 AC: 452 AN: 2110

Alfa AF: 0.289 Hom.: 4094

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
PhyloP100		-0.37
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: rs3213894; hg19: chr5-71528110;