1-175014871-T-TA

Variant names:

• chr1-175014871-T-TA
• NM_022100.3:c.205-21dupT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022100.3(MRPS14):​c.205-21dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRPS14 NM_022100.3 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.69

Genes affected

MRPS14 (HGNC:14049): (mitochondrial ribosomal protein S14) 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 S14P family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS14	NM_022100.3	c.205-21dupT		intron_variant	Intron 2 of 2	ENST00000476371.1	NP_071383.1
MRPS14	NR_037606.2	n.314-21dupT		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS14	ENST00000476371.1	c.205-21_205-20insT		intron_variant	Intron 2 of 2	1	NM_022100.3	ENSP00000420714.1
MRPS14	ENST00000367677.3	n.*114-21_*114-20insT		intron_variant	Intron 2 of 2	1		ENSP00000431220.1
MRPS14	ENST00000498253.1	n.-48_-47insT		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Combined oxidative phosphorylation deficiency 38 Uncertain:1

Oct 13, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant (GRCh38; NM_022100.3:c.205-21dup) results in 1 nucleotide duplication in the intronic region of the MRPS14 gene. Not observed at significant frequency in large population cohorts. A literature search was performed for the gene and associated variants. Based on this search no publications were found. In summary, this variant meets our criteria for classification as of Unknown Clinical Significance based on the evidence outlined. -

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-174984007;