3-139020282-A-C

Variant names:

• chr3-139020282-A-C
• rs766240382
• NM_001013650.2:c.380T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001013650.2(PRR23B):​c.380T>G​(p.Phe127Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRR23B NM_001013650.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200

Genes affected

PRR23B (HGNC:33764): (proline rich 23B)

MRPS22 (HGNC:14508): (mitochondrial ribosomal protein S22) 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 that does not seem to have a counterpart in prokaryotic and fungal-mitochondrial ribosomes. This gene lies telomeric of and is transcribed in the opposite direction from the forkhead box L2 gene. A pseudogene corresponding to this gene is found on chromosome Xq. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27383348).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR23B	NM_001013650.2	c.380T>G	p.Phe127Cys	missense_variant	Exon 1 of 1	ENST00000329447.5	NP_001013672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR23B	ENST00000329447.5	c.380T>G	p.Phe127Cys	missense_variant	Exon 1 of 1	6	NM_001013650.2	ENSP00000328768.5
MRPS22	ENST00000495075.5	c.-143+14187A>C		intron_variant	Intron 1 of 9	1		ENSP00000418008.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.091
Sift	Uncertain	0.019	D
Sift4G	Benign	0.083	T
Polyphen		0.058	B
Vest4		0.26
MutPred		0.65		Gain of catalytic residue at L128 (P = 0.0097);
MVP		0.030
MPC		1.8
ClinPred		0.56	D
GERP RS		0.35
Varity_R		0.13
gMVP		0.27

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

Other links and lift over

dbSNP: rs766240382; hg19: chr3-138739124;