8-79955124-C-T

Variant names:

• chr8-79955124-C-T
• rs6987013
• NM_014018.3:c.396-35976G>A

Variant summary

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

The NM_014018.3(MRPS28):​c.396-35976G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 152,094 control chromosomes in the GnomAD database, including 22,006 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 0.51 (22006 hom., cov: 32)
• Consequence: MRPS28 NM_014018.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 5 publications found

Genes affected

MRPS28 (HGNC:14513): (mitochondrial ribosomal protein S28) 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 has been called mitochondrial ribosomal protein S35 in the literature. [provided by RefSeq, Jul 2008]

MRPS28 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation deficiency 47

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000276418 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014018.3. 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
	MRPS28	NM_014018.3	MANE Select	c.396-35976G>A		intron	N/A	NP_054737.1
	TPD52-MRPS28	NM_001387778.1		c.618-35976G>A		intron	N/A	NP_001374707.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS28	ENST00000276585.9	TSL:1 MANE Select	c.396-35976G>A		intron	N/A	ENSP00000276585.4
	ENSG00000276418	ENST00000522938.5	TSL:2	n.*79+3133G>A		intron	N/A	ENSP00000430858.2
	MRPS28	ENST00000518271.1	TSL:5	c.462-35976G>A		intron	N/A	ENSP00000427846.1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77177 AN: 151976 Hom.: 22015 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.507 AC: 77181 AN: 152094 Hom.: 22006 Cov.: 32 AF XY: 0.515 AC XY: 38306 AN XY: 74338

African (AFR) AF: 0.237 AC: 9840 AN: 41502

American (AMR) AF: 0.460 AC: 7026 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2396 AN: 3472

East Asian (EAS) AF: 0.673 AC: 3473 AN: 5164

South Asian (SAS) AF: 0.643 AC: 3103 AN: 4828

European-Finnish (FIN) AF: 0.725 AC: 7661 AN: 10570

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41892 AN: 67968

Other (OTH) AF: 0.533 AC: 1126 AN: 2114

Alfa AF: 0.564 Hom.: 37524

Bravo AF: 0.472

Asia WGS AF: 0.597 AC: 2075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.1
DANN	Benign	0.78
PhyloP100		1.1
Mutation Taster		=100/0	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: rs6987013; hg19: chr8-80867359; COSMIC: COSV52562264; COSMIC: COSV52562264;