7-43866722-T-C

Variant names:

• chr7-43866722-T-C
• NM_032014.3:c.481A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032014.3(MRPS24):​c.481A>G​(p.Lys161Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRPS24 NM_032014.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60
• Publications: 0 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2834418).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032014.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS24	NM_032014.3	MANE Select	c.481A>G	p.Lys161Glu	missense	Exon 4 of 4	NP_114403.1	Q96EL2
	URGCP-MRPS24	NM_001204871.2		c.*284A>G		3_prime_UTR	Exon 7 of 7	NP_001191800.1	S4R325

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS24	ENST00000317534.6	TSL:1 MANE Select	c.481A>G	p.Lys161Glu	missense	Exon 4 of 4	ENSP00000318158.5	Q96EL2
	URGCP-MRPS24	ENST00000603700.1	TSL:5	c.*284A>G		3_prime_UTR	Exon 7 of 7	ENSP00000473871.1	S4R325
	MRPS24	ENST00000934254.1		c.397A>G	p.Lys133Glu	missense	Exon 4 of 4	ENSP00000604313.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0055	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.6
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.093
Sift	Benign	0.057	T
Sift4G	Uncertain	0.020	D
Polyphen		0.86	P
Vest4		0.43
MutPred		0.39		Loss of methylation at K161 (P = 0.0032)
MVP		0.60
MPC		0.63
ClinPred		0.80	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.44
gMVP		0.72
Mutation Taster		=67/33	polymorphism

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

Other links and lift over

hg19: chr7-43906321;