7-42932427-C-G

Variant names:

• chr7-42932427-C-G
• rs773548457
• NM_031903.3:c.41C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031903.3(MRPL32):​c.41C>G​(p.Ser14Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S14F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MRPL32 NM_031903.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81
• Publications: 0 publications found

Genes affected

MRPL32 (HGNC:14035): (mitochondrial ribosomal protein L32) 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 that belongs to the L32 ribosomal protein family. A pseudogene corresponding to this gene is found on chromosome Xp. [provided by RefSeq, Jul 2008]

ENSG00000256646 (HGNC:):

PSMA2 (HGNC:9531): (proteasome 20S subunit alpha 2) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the peptidase T1A family, that is a 20S core alpha subunit. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08705729).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031903.3. 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
	MRPL32	NM_031903.3	MANE Select	c.41C>G	p.Ser14Cys	missense	Exon 1 of 3	NP_114109.1	Q9BYC8
	MRPL32	NR_156497.1		n.52C>G		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL32	ENST00000223324.3	TSL:1 MANE Select	c.41C>G	p.Ser14Cys	missense	Exon 1 of 3	ENSP00000223324.2	Q9BYC8
	MRPL32	ENST00000900012.1		c.41C>G	p.Ser14Cys	missense	Exon 1 of 3	ENSP00000570071.1
	MRPL32	ENST00000921963.1		c.41C>G	p.Ser14Cys	missense	Exon 1 of 3	ENSP00000592022.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459902 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725906

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110570

Other (OTH) AF: 0.00 AC: 0 AN: 60282

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.8
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.030
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.021	D
Polyphen		0.14	B
Vest4		0.28
MutPred		0.43		Gain of catalytic residue at S14 (P = 0.0055)
MVP		0.16
MPC		0.076
ClinPred		0.24	T
GERP RS		3.3
PromoterAI		-0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.081
gMVP		0.19
Mutation Taster		=100/0	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

dbSNP: rs773548457; hg19: chr7-42972026;