4-83456050-C-T

Position:

• chr4-83456050-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000507019(MRPS18C):​c.-28C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 1,605,756 control chromosomes in the GnomAD database, including 7,256 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (3720 hom., cov: 31)
  • Exomes 𝑓: 0.013 (3536 hom.)
• Consequence: MRPS18C ENST00000507019 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308

Genes affected

MRPS18C (HGNC:16633): (mitochondrial ribosomal protein S18C) 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 S18P family. The encoded protein is one of three that has significant sequence similarity to bacterial S18 proteins. The primary sequences of the three human mitochondrial S18 proteins are no more closely related to each other than they are to the prokaryotic S18 proteins. Pseudogenes corresponding to this gene are found on chromosomes 8p, 12p, 15q, and 22q. [provided by RefSeq, Jul 2008]

MRPS18C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS18C	NM_016067.4	c.-28C>T		upstream_gene_variant		ENST00000295491.9	NP_057151.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS18C	ENST00000295491.9	c.-28C>T		upstream_gene_variant		1	NM_016067.4	ENSP00000295491.4

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18555 AN: 151940 Hom.: 3716 Cov.: 31

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0499

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00194

Gnomad OTH AF: 0.0920

GnomAD3 exomes AF: 0.0329 AC: 8261 AN: 251210 Hom.: 1555 AF XY: 0.0240 AC XY: 3262 AN XY: 135732

Gnomad AFR exome AF: 0.437

Gnomad AMR exome AF: 0.0221

Gnomad ASJ exome AF: 0.00576

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.000883

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00185

Gnomad OTH exome AF: 0.0149

GnomAD4 exome AF: 0.0133 AC: 19280 AN: 1453698 Hom.: 3536 Cov.: 31 AF XY: 0.0117 AC XY: 8434 AN XY: 723538

Gnomad4 AFR exome AF: 0.448

Gnomad4 AMR exome AF: 0.0254

Gnomad4 ASJ exome AF: 0.00682

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00107

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000992

Gnomad4 OTH exome AF: 0.0288

GnomAD4 genome AF: 0.122 AC: 18597 AN: 152058 Hom.: 3720 Cov.: 31 AF XY: 0.117 AC XY: 8722 AN XY: 74330

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.0498

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00194

Gnomad4 OTH AF: 0.0910

Alfa AF: 0.0414 Hom.: 260

Bravo AF: 0.139

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.9
DANN	Benign	0.82

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: rs3182340; hg19: chr4-84377203; COSMIC: COSV55025073; COSMIC: COSV55025073;