chr7-43869371-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001204871.2(URGCP-MRPS24):​c.181G>A​(p.Val61Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,549,678 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: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

URGCP-MRPS24
NM_001204871.2 missense

Scores

9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.541
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07270369).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPS24NM_032014.3 linkc.45G>A p.Leu15Leu synonymous_variant Exon 2 of 4 ENST00000317534.6 NP_114403.1 Q96EL2
URGCP-MRPS24NM_001204871.2 linkc.181G>A p.Val61Ile missense_variant Exon 5 of 7 NP_001191800.1 S4R325

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
URGCP-MRPS24ENST00000603700.1 linkc.181G>A p.Val61Ile missense_variant Exon 5 of 7 5 ENSP00000473871.1 S4R325
MRPS24ENST00000317534.6 linkc.45G>A p.Leu15Leu synonymous_variant Exon 2 of 4 1 NM_032014.3 ENSP00000318158.5 Q96EL2

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152204
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000220
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000955
AC:
14
AN:
146648
Hom.:
0
AF XY:
0.000115
AC XY:
9
AN XY:
78544
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.000243
Gnomad OTH exome
AF:
0.000235
GnomAD4 exome
AF:
0.000182
AC:
255
AN:
1397474
Hom.:
0
Cov.:
35
AF XY:
0.000161
AC XY:
111
AN XY:
689262
show subpopulations
Gnomad4 AFR exome
AF:
0.0000633
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:
0.000228
Gnomad4 OTH exome
AF:
0.000121
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152204
Hom.:
0
Cov.:
33
AF XY:
0.0000807
AC XY:
6
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000220
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000676
Hom.:
0
Bravo
AF:
0.000155
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000390
AC:
3
ExAC
AF:
0.0000118
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 03, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.181G>A (p.V61I) alteration is located in exon 5 (coding exon 5) of the URGCP-MRPS24 gene. This alteration results from a G to A substitution at nucleotide position 181, causing the valine (V) at amino acid position 61 to be replaced by an isoleucine (I). 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
-0.54
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
10
DANN
Benign
0.87
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.31
T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.073
T
Sift4G
Benign
0.68
T
Vest4
0.052
MVP
0.46
MPC
0.74
GERP RS
1.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs376705600; hg19: chr7-43908970; API