5-72221085-T-G

Variant names:

• chr5-72221085-T-G
• rs141373207
• NM_015084.3:c.1069A>C

Variant summary

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

The NM_015084.3(MRPS27):​c.1069A>C​(p.Thr357Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T357A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MRPS27 NM_015084.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1069A>C	p.Thr357Pro	missense	Exon 11 of 11	NP_055899.2	Q92552-1
	MRPS27	NM_001286748.2		c.1111A>C	p.Thr371Pro	missense	Exon 12 of 12	NP_001273677.1	Q92552-2
	MRPS27	NM_001286751.2		c.901A>C	p.Thr301Pro	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.1069A>C	p.Thr357Pro	missense	Exon 11 of 11	ENSP00000261413.5	Q92552-1
	MRPS27	ENST00000695404.1		c.1069A>C	p.Thr357Pro	missense	Exon 11 of 12	ENSP00000511886.1	A0A8Q3WKF1
	MRPS27	ENST00000694998.2		c.1135A>C	p.Thr379Pro	missense	Exon 11 of 11	ENSP00000511636.2	A0A8Q3WK88

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461850 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727220

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111982

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.081	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.6
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.30
Sift	Benign	0.039	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.98	D
Vest4		0.42
MutPred		0.79		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.66
MPC		0.42
ClinPred		0.88	D
GERP RS		3.7
Varity_R		0.35
gMVP		0.57
Mutation Taster		=73/27	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: rs141373207; hg19: chr5-71516912;