5-72221038-G-C

Variant names:

• chr5-72221038-G-C
• rs369816290
• NM_015084.3:c.1116C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015084.3(MRPS27):​c.1116C>G​(p.Ile372Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000431 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: MRPS27 NM_015084.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.373
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09206623).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS27	NM_015084.3	MANE Select	c.1116C>G	p.Ile372Met	missense	Exon 11 of 11	NP_055899.2	Q92552-1
	MRPS27	NM_001286748.2		c.1158C>G	p.Ile386Met	missense	Exon 12 of 12	NP_001273677.1	Q92552-2
	MRPS27	NM_001286751.2		c.948C>G	p.Ile316Met	missense	Exon 11 of 11	NP_001273680.1	G5EA06

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS27	ENST00000261413.10	TSL:1 MANE Select	c.1116C>G	p.Ile372Met	missense	Exon 11 of 11	ENSP00000261413.5	Q92552-1
	MRPS27	ENST00000695404.1		c.1116C>G	p.Ile372Met	missense	Exon 11 of 12	ENSP00000511886.1	A0A8Q3WKF1
	MRPS27	ENST00000694998.2		c.1182C>G	p.Ile394Met	missense	Exon 11 of 11	ENSP00000511636.2	A0A8Q3WK88

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251166 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000431 AC: 63 AN: 1461858 Hom.: 0 Cov.: 31 AF XY: 0.0000440 AC XY: 32 AN XY: 727230

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000504 AC: 56 AN: 1111992

Other (OTH) AF: 0.0000662 AC: 4 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000152 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.96
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.65	N
PhyloP100		-0.37
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.052
Sift	Benign	0.091	T
Sift4G	Benign	0.19	T
Polyphen		0.11	B
Vest4		0.12
MutPred		0.47		Gain of disorder (P = 0.0464)
MVP		0.18
MPC		0.099
ClinPred		0.071	T
GERP RS		-5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.036
gMVP		0.31
Mutation Taster		=92/8	polymorphism

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: rs369816290; hg19: chr5-71516865;