chr8-80030026-C-CGGGCTCCACCTTCTGTAG

Variant names:

• chr8-80030026-C-CGGGCTCCACCTTCTGTAG
• NM_014018.3:c.205_213+9dupCTACAGAAGGTGGAGCCC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_014018.3(MRPS28):​c.205_213+9dupCTACAGAAGGTGGAGCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,609,978 control chromosomes in the GnomAD database, including 17 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0023 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (13 hom.)
• Consequence: MRPS28 NM_014018.3 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.75

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]

ENSG00000276418 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 8-80030026-C-CGGGCTCCACCTTCTGTAG is Benign according to our data. Variant chr8-80030026-C-CGGGCTCCACCTTCTGTAG is described in ClinVar as [Likely_benign]. Clinvar id is 3038476.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS28	NM_014018.3	c.205_213+9dupCTACAGAAGGTGGAGCCC		intron_variant	Intron 1 of 2	ENST00000276585.9	NP_054737.1
TPD52-MRPS28	NM_001387778.1	c.435+12576_435+12593dupCTACAGAAGGTGGAGCCC		intron_variant	Intron 5 of 6		NP_001374707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS28	ENST00000276585.9	c.213+9_213+10insCTACAGAAGGTGGAGCCC		intron_variant	Intron 1 of 2	1	NM_014018.3	ENSP00000276585.4
ENSG00000276418	ENST00000522938.5	n.555+12593_555+12594insCTACAGAAGGTGGAGCCC		intron_variant	Intron 5 of 7	2		ENSP00000430858.2

Frequencies

GnomAD3 genomes AF: 0.00225 AC: 341 AN: 151764 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00336

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.00127 AC: 314 AN: 246720 Hom.: 2 AF XY: 0.00127 AC XY: 170 AN XY: 133598

Gnomad AFR exome AF: 0.00225

Gnomad AMR exome AF: 0.000525

Gnomad ASJ exome AF: 0.000803

Gnomad EAS exome AF: 0.00280

Gnomad SAS exome AF: 0.000823

Gnomad FIN exome AF: 0.00565

Gnomad NFE exome AF: 0.000502

Gnomad OTH exome AF: 0.000662

GnomAD4 exome AF: 0.00134 AC: 1957 AN: 1458096 Hom.: 13 Cov.: 31 AF XY: 0.00137 AC XY: 991 AN XY: 725144

Gnomad4 AFR exome AF: 0.00294

Gnomad4 AMR exome AF: 0.000562

Gnomad4 ASJ exome AF: 0.000959

Gnomad4 EAS exome AF: 0.00202

Gnomad4 SAS exome AF: 0.000953

Gnomad4 FIN exome AF: 0.00710

Gnomad4 NFE exome AF: 0.00102

Gnomad4 OTH exome AF: 0.00223

GnomAD4 genome AF: 0.00226 AC: 343 AN: 151882 Hom.: 4 Cov.: 32 AF XY: 0.00287 AC XY: 213 AN XY: 74292

Gnomad4 AFR AF: 0.00340

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.000779

Gnomad4 OTH AF: 0.000948

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MRPS28-related disorder Benign:1

Dec 05, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-80942261;