chr3-15065088-G-A

Variant names:

• chr3-15065088-G-A
• rs750388546
• NM_022497.5:c.107C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022497.5(MRPS25):​c.107C>T​(p.Thr36Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,452,932 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: MRPS25 NM_022497.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.32

Genes affected

MRPS25 (HGNC:14511): (mitochondrial ribosomal protein S25) 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. A pseudogene corresponding to this gene is found on chromosome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ENSG00000289750 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS25	NM_022497.5	c.107C>T	p.Thr36Met	missense_variant	Exon 1 of 4	ENST00000253686.7	NP_071942.1
MRPS25	NR_135246.2	n.228C>T		non_coding_transcript_exon_variant	Exon 1 of 5
MRPS25	NR_135247.2	n.228C>T		non_coding_transcript_exon_variant	Exon 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS25	ENST00000253686.7	c.107C>T	p.Thr36Met	missense_variant	Exon 1 of 4	1	NM_022497.5	ENSP00000253686.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000857 AC: 2 AN: 233316 Hom.: 0 AF XY: 0.0000158 AC XY: 2 AN XY: 126504

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 SAS exome AF: 0.0000695

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1452932 Hom.: 0 Cov.: 31 AF XY: 0.00000415 AC XY: 3 AN XY: 722074

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000236

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.;.
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Uncertain	-0.093	T
MutationAssessor	Uncertain	2.2	M;M;M
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Benign	0.28
Sift	Benign	0.050	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.71
MutPred		0.32		Gain of catalytic residue at V32 (P = 0.0951);Gain of catalytic residue at V32 (P = 0.0951);Gain of catalytic residue at V32 (P = 0.0951);
MVP		0.24
MPC		0.37
ClinPred		0.93	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs750388546; hg19: chr3-15106595;