rs749889500

Variant names:

• chr5-72223847-C-A
• rs749889500
• NM_015084.3:c.841G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-72223847-C-A
• chr5-72223847-C-T

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.841G>T​(p.Asp281Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D281N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: MRPS27 NM_015084.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.551
• Publications: 1 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=0.24124554).

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.841G>T	p.Asp281Tyr	missense	Exon 10 of 11	NP_055899.2	Q92552-1
	MRPS27	NM_001286748.2		c.883G>T	p.Asp295Tyr	missense	Exon 11 of 12	NP_001273677.1	Q92552-2
	MRPS27	NM_001286751.2		c.673G>T	p.Asp225Tyr	missense	Exon 10 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.841G>T	p.Asp281Tyr	missense	Exon 10 of 11	ENSP00000261413.5	Q92552-1
	MRPS27	ENST00000522562.5	TSL:1	n.*269G>T		non_coding_transcript_exon	Exon 7 of 7	ENSP00000511937.1	A0A8Q3WKM3
	MRPS27	ENST00000522562.5	TSL:1	n.*269G>T		3_prime_UTR	Exon 7 of 7	ENSP00000511937.1	A0A8Q3WKM3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000800 AC: 2 AN: 250074 AF XY: 0.0000148

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460938 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 726696

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111424

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000247 AC: 3

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	0.15
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.55
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.091
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.51		Loss of disorder (P = 0.0205)
MVP		0.42
MPC		0.42
ClinPred		0.87	D
GERP RS		1.5
Varity_R		0.13
gMVP		0.55
Mutation Taster		=85/15	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: rs749889500; hg19: chr5-71519674;