1-156738543-C-G

Variant names:

• chr1-156738543-C-G
• rs749677650
• NM_145729.3:c.162G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_145729.3(MRPL24):​c.162G>C​(p.Trp54Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: MRPL24 NM_145729.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.07
• Publications: 0 publications found

Genes affected

MRPL24 (HGNC:14037): (mitochondrial ribosomal protein L24) 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 39S subunit protein which is more than twice the size of its E.coli counterpart (EcoL24). Sequence analysis identified two transcript variants that encode the same protein. [provided by RefSeq, Jul 2008]

ACMG classification

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

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.81

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145729.3. 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
	MRPL24	NM_145729.3	MANE Select	c.162G>C	p.Trp54Cys	missense	Exon 2 of 6	NP_663781.1	Q96A35
	MRPL24	NM_024540.4		c.162G>C	p.Trp54Cys	missense	Exon 2 of 6	NP_078816.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL24	ENST00000361531.6	TSL:1 MANE Select	c.162G>C	p.Trp54Cys	missense	Exon 2 of 6	ENSP00000354525.2	Q96A35
	MRPL24	ENST00000368211.8	TSL:1	c.162G>C	p.Trp54Cys	missense	Exon 2 of 6	ENSP00000357194.4	Q96A35
	MRPL24	ENST00000915502.1		c.162G>C	p.Trp54Cys	missense	Exon 2 of 6	ENSP00000585561.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251420 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461864 Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000224 AC: 10 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

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	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.1
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-12	D
REVEL	Uncertain	0.54
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.64		Loss of catalytic residue at W54 (P = 0.0056)
MVP		0.36
MPC		1.1
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.95
gMVP		0.91
Mutation Taster		=13/87	disease causing

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

dbSNP: rs749677650; hg19: chr1-156708335;