3-139005884-C-T

Variant names:

• chr3-139005884-C-T
• rs147495715
• NM_001134659.1:c.385G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001134659.1(PRR23A):​c.385G>A​(p.Gly129Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 31)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: PRR23A NM_001134659.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

Genes affected

PRR23A (HGNC:37172): (proline rich 23A)

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1665074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR23A	NM_001134659.1	c.385G>A	p.Gly129Ser	missense_variant	Exon 1 of 1	ENST00000383163.4	NP_001128131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR23A	ENST00000383163.4	c.385G>A	p.Gly129Ser	missense_variant	Exon 1 of 1	6	NM_001134659.1	ENSP00000372649.2
MRPS22	ENST00000495075	c.-354C>T		5_prime_UTR_variant	Exon 1 of 10	1		ENSP00000418008.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000157 AC: 23 AN: 1461308 Hom.: 0 Cov.: 53 AF XY: 0.0000138 AC XY: 10 AN XY: 726890

Gnomad4 AFR exome AF: 0.00

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: 0.0000189

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.1
DANN	Benign	0.96
DEOGEN2	Benign	0.0058	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0038	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.77	N
REVEL	Benign	0.16
Sift	Benign	0.73	T
Sift4G	Benign	0.75	T
Polyphen		0.99	D
Vest4		0.057
MutPred		0.66		Gain of helix (P = 0.0325);
MVP		0.030
MPC		1.4
ClinPred		0.52	D
GERP RS		-4.4
Varity_R		0.024
gMVP		0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs147495715; hg19: chr3-138724726;