2-95090432-T-C

Variant names:

• chr2-95090432-T-C
• NM_031902.5:c.1022A>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_031902.5(MRPS5):​c.1022A>G​(p.Asn341Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRPS5 NM_031902.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.75

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS5	NM_031902.5	c.1022A>G	p.Asn341Ser	missense_variant	Exon 11 of 12	ENST00000272418.7	NP_114108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS5	ENST00000272418.7	c.1022A>G	p.Asn341Ser	missense_variant	Exon 11 of 12	1	NM_031902.5	ENSP00000272418.2
ENSG00000289685	ENST00000695456.1	n.*1901A>G		non_coding_transcript_exon_variant	Exon 16 of 17			ENSP00000511928.1
ENSG00000289685	ENST00000695456.1	n.*1901A>G		3_prime_UTR_variant	Exon 16 of 17			ENSP00000511928.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1022A>G (p.N341S) alteration is located in exon 11 (coding exon 11) of the MRPS5 gene. This alteration results from a A to G substitution at nucleotide position 1022, causing the asparagine (N) at amino acid position 341 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.042	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.28
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.049	D
Polyphen		0.95	P
Vest4		0.73
MutPred		0.67		Gain of disorder (P = 0.1033);
MVP		0.81
MPC		0.46
ClinPred		0.99	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-95756177;