chr2-95101696-C-T

Variant names:

• chr2-95101696-C-T
• rs150829989
• NM_031902.5:c.791G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_031902.5(MRPS5):​c.791G>A​(p.Arg264Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000159 in 1,599,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: MRPS5 NM_031902.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.47
• Publications: 3 publications found

Genes affected

MRPS5 (HGNC:14498): (mitochondrial ribosomal protein S5) 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 belongs to the ribosomal protein S5P family. Pseudogenes corresponding to this gene are found on chromosomes 4q, 5q, and 18q. [provided by RefSeq, Jul 2008]

ENSG00000289685 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.38023606).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031902.5. 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
	MRPS5	NM_031902.5	MANE Select	c.791G>A	p.Arg264Gln	missense	Exon 8 of 12	NP_114108.1	P82675-1
	MRPS5	NM_001321995.2		c.554G>A	p.Arg185Gln	missense	Exon 8 of 12	NP_001308924.1	A0A8Q3SIP9
	MRPS5	NM_001321996.2		c.293G>A	p.Arg98Gln	missense	Exon 8 of 12	NP_001308925.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS5	ENST00000272418.7	TSL:1 MANE Select	c.791G>A	p.Arg264Gln	missense	Exon 8 of 12	ENSP00000272418.2	P82675-1
	ENSG00000289685	ENST00000695456.1		n.*1670G>A		non_coding_transcript_exon	Exon 13 of 17	ENSP00000511928.1
	ENSG00000289685	ENST00000695456.1		n.*1670G>A		3_prime_UTR	Exon 13 of 17	ENSP00000511928.1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000102 AC: 24 AN: 235792 AF XY: 0.0000941

Gnomad AFR exome AF: 0.0000641

Gnomad AMR exome AF: 0.0000659

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000187

Gnomad NFE exome AF: 0.000128

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000160 AC: 231 AN: 1447302 Hom.: 0 Cov.: 29 AF XY: 0.000154 AC XY: 111 AN XY: 719724

African (AFR) AF: 0.0000619 AC: 2 AN: 32314

American (AMR) AF: 0.0000497 AC: 2 AN: 40254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25554

East Asian (EAS) AF: 0.00 AC: 0 AN: 39486

South Asian (SAS) AF: 0.0000846 AC: 7 AN: 82704

European-Finnish (FIN) AF: 0.000244 AC: 13 AN: 53230

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5682

European-Non Finnish (NFE) AF: 0.000184 AC: 204 AN: 1108342

Other (OTH) AF: 0.0000335 AC: 2 AN: 59736

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152108 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74308

African (AFR) AF: 0.0000966 AC: 4 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000149 Hom.: 0

Bravo AF: 0.0000945

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000148 AC: 18

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	0.24
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	24
DANN	Benign	0.46
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.099
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.0	L
PhyloP100		5.5
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.23
Sift	Benign	0.31	T
Sift4G	Benign	0.67	T
Polyphen		0.035	B
Vest4		0.69
MVP		0.56
MPC		0.18
ClinPred		0.077	T
GERP RS		5.3
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.12
gMVP		0.76
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs150829989; hg19: chr2-95767441; COSMIC: COSV55532612; COSMIC: COSV55532612;