6-43686799-G-C

Position:

• chr6-43686799-G-C

Variant summary

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

The NM_018135.4(MRPS18A):​c.112+869C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,152 control chromosomes in the GnomAD database, including 6,246 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 0.26 (6246 hom., cov: 33)
• Consequence: MRPS18A NM_018135.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251

Genes affected

MRPS18A (HGNC:14515): (mitochondrial ribosomal protein S18A) 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. A pseudogene corresponding to this gene is found on chromosome 3p. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jul 2010]

POLR1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPS18A	NM_018135.4	c.112+869C>G		intron_variant		ENST00000372133.8
MRPS18A	NM_001193343.2	c.112+869C>G		intron_variant
POLR1C	NM_001318876.2	c.945+157528G>C		intron_variant
MRPS18A	XM_006715134.4	c.112+869C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPS18A	ENST00000372133.8	c.112+869C>G		intron_variant		1	NM_018135.4	P1
MRPS18A	ENST00000427312.1	c.112+869C>G		intron_variant		1
MRPS18A	ENST00000372116.5	c.112+869C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38909 AN: 152034 Hom.: 6242 Cov.: 33

Gnomad AFR AF: 0.0761

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.260

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.256 AC: 38909 AN: 152152 Hom.: 6246 Cov.: 33 AF XY: 0.260 AC XY: 19354 AN XY: 74384

Gnomad4 AFR AF: 0.0759

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.0266

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.256

Alfa AF: 0.179 Hom.: 436

Bravo AF: 0.245

Asia WGS AF: 0.133 AC: 461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.73

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: rs833048; hg19: chr6-43654536;