NM_014018.3:c.213+9_213+10insCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCC

Variant names:

• chr8-80030026-C-CGGGCTCCACCTTCTGTAGGGGCTCCACCTTCTGTAGGGGCTCCACCTTCTGTAGGGGCTCCACCTTCTGTAG
• NM_014018.3:c.213+9_213+10insCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCC

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6

The NM_014018.3(MRPS28):​c.213+9_213+10insCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000062 (0 hom.)
  • Failed GnomAD Quality Control
• 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 -1 ACMG points.

• BP6: Variant 8-80030026-C-CGGGCTCCACCTTCTGTAGGGGCTCCACCTTCTGTAGGGGCTCCACCTTCTGTAGGGGCTCCACCTTCTGTAG is Benign according to our data. Variant chr8-80030026-C-CGGGCTCCACCTTCTGTAGGGGCTCCACCTTCTGTAGGGGCTCCACCTTCTGTAGGGGCTCCACCTTCTGTAG is described in ClinVar as [Likely_benign]. Clinvar id is 3039901.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS28	NM_014018.3	c.213+9_213+10insCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCC		intron_variant	Intron 1 of 2	ENST00000276585.9	NP_054737.1
TPD52-MRPS28	NM_001387778.1	c.435+12593_435+12594insCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCC		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+10insCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCC		intron_variant	Intron 1 of 2	1	NM_014018.3	ENSP00000276585.4
ENSG00000276418	ENST00000522938.5	n.555+12593_555+12594insCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCCCTACAGAAGGTGGAGCCC		intron_variant	Intron 5 of 7	2		ENSP00000430858.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 225 AN: 151768 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00524

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.000122 AC: 30 AN: 246720 Hom.: 0 AF XY: 0.0000674 AC XY: 9 AN XY: 133598

Gnomad AFR exome AF: 0.00174

Gnomad AMR exome AF: 0.0000583

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000165

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000617 AC: 90 AN: 1458108 Hom.: 0 Cov.: 31 AF XY: 0.0000441 AC XY: 32 AN XY: 725146

Gnomad4 AFR exome AF: 0.00187

Gnomad4 AMR exome AF: 0.000247

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000282

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00147 AC: 224 AN: 151886 Hom.: 0 Cov.: 32 AF XY: 0.00125 AC XY: 93 AN XY: 74296

Gnomad4 AFR AF: 0.00520

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00190

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MRPS28-related disorder Benign:1

Jul 24, 2022

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;