Variant rs746575859 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031420.4(MRPL9):c.20C>T(p.Thr7Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000352 in 1,422,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. T7R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

MRPL9
NM_031420.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.359

Variant links:

Genes affected

MRPL9 (HGNC:14277): (mitochondrial ribosomal protein L9) This is a nuclear gene encoding a protein component of the 39S subunit of the mitochondrial ribosome. Alternative splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 8. [provided by RefSeq, Jul 2014]

MRPL9 links:

OAZ3 (HGNC:8097): (ornithine decarboxylase antizyme 3) The protein encoded by this gene belongs to the ornithine decarboxylase antizyme family, which plays a role in cell growth and proliferation by regulating intracellular polyamine levels. Expression of antizymes requires +1 ribosomal frameshifting, which is enhanced by high levels of polyamines. Antizymes in turn bind to and inhibit ornithine decarboxylase (ODC), the key enzyme in polyamine biosynthesis; thus, completing the auto-regulatory circuit. This gene encodes antizyme 3, the third member of the antizyme family. Like antizymes 1 and 2, antizyme 3 inhibits ODC activity and polyamine uptake; however, it does not stimulate ODC degradation. Also, while antizymes 1 and 2 have broad tissue distribution, expression of antizyme 3 is restricted to haploid germ cells in testis, suggesting a distinct role for this antizyme in spermiogenesis. Antizyme 3 gene knockout studies showed that homozygous mutant male mice were infertile, and indicated the likely role of this antizyme in the formation of a rigid connection between the sperm head and tail during spermatogenesis. Alternatively spliced transcript variants encoding different isoforms, including one resulting from the use of non-AUG (CUG) translation initiation codon, have been found for this gene. [provided by RefSeq, Dec 2014]

OAZ3 links:

ENSG00000249602 (HGNC:):

ENSG00000249602 links:

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ACMG classification

Classification made for transcript

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=0.08757764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL9	NM_031420.4 link	c.20C>T	p.Thr7Met	missense_variant	Exon 1 of 7	ENST00000368830.8	NP_113608.1	Q9BYD2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MRPL9	ENST00000368830.8 link	c.20C>T	p.Thr7Met	missense_variant	Exon 1 of 7	1	NM_031420.4	ENSP00000357823.3	Q9BYD2
OAZ3	ENST00000321531.10 link	c.32+293G>A		intron_variant	Intron 1 of 5	5		ENSP00000313922.5	A0A0G2JH29
OAZ3	ENST00000635322.1 link	c.32+293G>A		intron_variant	Intron 1 of 4	5		ENSP00000489350.1	A0A0U1RR57
OAZ3	ENST00000453029.2 link	c.-35G>A		upstream_gene_variant		5		ENSP00000415904.2	H0Y7Y4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000548

AC:

AN:

182588

Hom.:

AF XY:

0.0000101

AC XY:

AN XY:

99214

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000130

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000352

AC:

AN:

1422114

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

703764

show subpopulations

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:

0.00000458

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000244

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0012

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0041

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.088

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.39

N;N

REVEL

Benign

0.040

Sift

Uncertain

0.027

D;D

Sift4G

Uncertain

0.058

T;T

Polyphen

0.012

B;.

Vest4

0.17

MutPred

0.26

Loss of glycosylation at T7 (P = 0.0305);Loss of glycosylation at T7 (P = 0.0305);

MVP

0.12

MPC

0.56

ClinPred

0.067

GERP RS

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.024

gMVP

0.45

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over