4-83456050-C-T

Variant names:

• chr4-83456050-C-T
• rs3182340
• ENST00000507019.5:c.-28C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000507019.5(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 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• Publications: 7 publications found

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]

HELQ (HGNC:18536): (helicase, POLQ like) HEL308 is a single-stranded DNA-dependent ATPase and DNA helicase (Marini and Wood, 2002 [PubMed 11751861]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000507019.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HELQ	NM_133636.5	MANE Select	c.-357G>A		upstream_gene	N/A	NP_598375.3
	MRPS18C	NM_016067.4	MANE Select	c.-28C>T		upstream_gene	N/A	NP_057151.1
	HELQ	NM_001297755.2		c.-357G>A		upstream_gene	N/A	NP_001284684.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS18C	ENST00000507019.5	TSL:2	c.-28C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000427169.1
	MRPS18C	ENST00000512375.1	TSL:2	n.119C>T		non_coding_transcript_exon	Exon 1 of 2
	MRPS18C	ENST00000507019.5	TSL:2	c.-28C>T		5_prime_UTR	Exon 1 of 5	ENSP00000427169.1

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

GnomAD2 exomes AF: 0.0329 AC: 8261 AN: 251210 AF XY: 0.0240

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 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

African (AFR) AF: 0.448 AC: 14897 AN: 33268

American (AMR) AF: 0.0254 AC: 1137 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00682 AC: 178 AN: 26094

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39672

South Asian (SAS) AF: 0.00107 AC: 92 AN: 85974

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53416

Middle Eastern (MID) AF: 0.0341 AC: 142 AN: 4168

European-Non Finnish (NFE) AF: 0.000992 AC: 1098 AN: 1106342

Other (OTH) AF: 0.0288 AC: 1732 AN: 60048

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

African (AFR) AF: 0.422 AC: 17470 AN: 41380

American (AMR) AF: 0.0498 AC: 762 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.00194 AC: 132 AN: 68002

Other (OTH) AF: 0.0910 AC: 192 AN: 2110

Alfa AF: 0.0497 Hom.: 317

Bravo AF: 0.139

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.9
DANN	Benign	0.82
PhyloP100		-0.31
PromoterAI		-0.15	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

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