5-44809446-C-G

Variant names:

• chr5-44809446-C-G
• rs146658127
• NM_016640.4:c.484C>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_016640.4(MRPS30):​c.484C>G​(p.Arg162Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000628 in 1,613,770 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00067 (2 hom.)
• Consequence: MRPS30 NM_016640.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72

Genes affected

MRPS30 (HGNC:8769): (mitochondrial ribosomal protein S30) 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 is similar to the chicken pro-apoptotic protein p52. Transcript variants using alternative promoters or polyA sites have been mentioned in the literature but the complete description of these sequences is not available. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11811006).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS30	NM_016640.4	c.484C>G	p.Arg162Gly	missense_variant	Exon 1 of 5	ENST00000507110.6	NP_057724.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS30	ENST00000507110.6	c.484C>G	p.Arg162Gly	missense_variant	Exon 1 of 5	1	NM_016640.4	ENSP00000424328.1

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152190 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000321 AC: 80 AN: 249344 Hom.: 1 AF XY: 0.000347 AC XY: 47 AN XY: 135268

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000948

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.000409

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000666 AC: 973 AN: 1461462 Hom.: 2 Cov.: 32 AF XY: 0.000703 AC XY: 511 AN XY: 727044

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000707

Gnomad4 FIN exome AF: 0.0000753

Gnomad4 NFE exome AF: 0.000787

Gnomad4 OTH exome AF: 0.000414

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152308 Hom.: 0 Cov.: 33 AF XY: 0.000228 AC XY: 17 AN XY: 74476

Gnomad4 AFR AF: 0.000216

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000367

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000342 Hom.: 0

Bravo AF: 0.000287

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000519 AC: 2

ExAC AF: 0.000313 AC: 38

EpiCase AF: 0.000600

EpiControl AF: 0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 03, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.484C>G (p.R162G) alteration is located in exon 1 (coding exon 1) of the MRPS30 gene. This alteration results from a C to G substitution at nucleotide position 484, causing the arginine (R) at amino acid position 162 to be replaced by a glycine (G). 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	0.091
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.88
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.094
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.23
Sift	Benign	0.20	T
Sift4G	Benign	0.54	T
Polyphen		1.0	D
Vest4		0.44
MVP		0.24
MPC		0.76
ClinPred		0.22	T
GERP RS		4.8
Varity_R		0.57
gMVP		0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs146658127; hg19: chr5-44809548;