7-43869045-C-T

Variant names:

• chr7-43869045-C-T
• ENST00000603700.1:c.274G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001204871.2(URGCP-MRPS24):​c.274G>A​(p.Gly92Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: URGCP-MRPS24 NM_001204871.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0960

Genes affected

URGCP-MRPS24 (HGNC:49188): (URGCP-MRPS24 readthrough) This locus represents naturally occurring read-through transcription between the neighboring URGCP (upregulator of cell proliferation) and MRPS24 (mitochondrial ribosomal protein S24) genes on chromosome 7. The read-through transcript is predicted to encode a protein that shares sequence identity with the upstream gene product but its C-terminal region is distinct due to a frameshift relative to the downstream gene. [provided by RefSeq, Mar 2011]

MRPS24 (HGNC:14510): (mitochondrial ribosomal protein S24) 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. A pseudogene corresponding to this gene is found on chromosome 11. Read-through transcription exists between this gene and the upstream upregulator of cell proliferation (URGCP) gene. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19153792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS24	NM_032014.3	c.138G>A	p.Lys46Lys	synonymous_variant	Exon 3 of 4	ENST00000317534.6	NP_114403.1
URGCP-MRPS24	NM_001204871.2	c.274G>A	p.Gly92Arg	missense_variant	Exon 6 of 7		NP_001191800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
URGCP-MRPS24	ENST00000603700.1	c.274G>A	p.Gly92Arg	missense_variant	Exon 6 of 7	5		ENSP00000473871.1
MRPS24	ENST00000317534.6	c.138G>A	p.Lys46Lys	synonymous_variant	Exon 3 of 4	1	NM_032014.3	ENSP00000318158.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461246 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726942

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.274G>A (p.G92R) alteration is located in exon 6 (coding exon 6) of the URGCP-MRPS24 gene. This alteration results from a G to A substitution at nucleotide position 274, causing the glycine (G) at amino acid position 92 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	7.4
DANN	Benign	0.87
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.19	T
Vest4		0.38
MVP		0.41
MPC		1.1
GERP RS		-0.17

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: chr7-43908644;