Variant 2-105088985-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_182640.3(MRPS9):c.491A>C(p.Asp164Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000138 in 1,453,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MRPS9
NM_182640.3 missense, splice_region

Scores

Splicing: ADA: 0.02286

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.35

Variant links:

Genes affected

MRPS9 (HGNC:14501): (mitochondrial ribosomal protein S9) 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. [provided by RefSeq, Jul 2008]

MRPS9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MRPS9	NM_182640.3 linkuse as main transcript	c.491A>C	p.Asp164Ala	missense_variant, splice_region_variant	6/11	ENST00000258455.8	NP_872578.1
MRPS9	XM_011511644.3 linkuse as main transcript	c.119A>C	p.Asp40Ala	missense_variant, splice_region_variant	5/10		XP_011509946.1
MRPS9	XM_047445533.1 linkuse as main transcript	c.491A>C	p.Asp164Ala	missense_variant, splice_region_variant	6/7		XP_047301489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS9	ENST00000258455.8 linkuse as main transcript	c.491A>C	p.Asp164Ala	missense_variant, splice_region_variant	6/11	1	NM_182640.3	ENSP00000258455	P1
MRPS9	ENST00000413583.5 linkuse as main transcript			upstream_gene_variant		3		ENSP00000388885

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249652

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135052

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS 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:

0.00000138

AC:

AN:

1453070

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

723248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 06, 2023

The c.491A>C (p.D164A) alteration is located in exon 6 (coding exon 6) of the MRPS9 gene. This alteration results from a A to C substitution at nucleotide position 491, causing the aspartic acid (D) at amino acid position 164 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.080

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.79

MetaSVM

Uncertain

0.56

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-5.4

REVEL

Uncertain

0.52

Sift

Uncertain

0.012

Sift4G

Uncertain

0.033

Polyphen

0.58

Vest4

0.32

MutPred

0.80

Loss of phosphorylation at Y166 (P = 0.0755);

MVP

0.97

MPC

0.56

ClinPred

0.94

GERP RS

6.1

Varity_R

0.28

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.023

dbscSNV1_RF

Benign

0.10

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over