chr8-79955124-C-T

Position:

• chr8-79955124-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

TPD52-MRPS28 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPS28	NM_014018.3	c.396-35976G>A		intron_variant		ENST00000276585.9
TPD52-MRPS28	NM_001387778.1	c.618-35976G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPS28	ENST00000276585.9	c.396-35976G>A		intron_variant		1	NM_014018.3	P1

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

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.643

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.533

Alfa AF: 0.579 Hom.: 26866

Bravo AF: 0.472

Asia WGS AF: 0.597 AC: 2075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.1
DANN	Benign	0.78

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: rs6987013; hg19: chr8-80867359; COSMIC: COSV52562264; COSMIC: COSV52562264;