Variant 2-105092483-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_182640.3(MRPS9):c.734G>A(p.Arg245Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00545 in 1,613,906 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0056 ( 27 hom. )

Consequence

MRPS9
NM_182640.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.88

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:

MRPS9-AS1 (HGNC:40688): (MRPS9 antisense RNA 1)

MRPS9-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010786384).

BP6

Variant 2-105092483-G-A is Benign according to our data. Variant chr2-105092483-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651226.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS9	NM_182640.3 linkuse as main transcript	c.734G>A	p.Arg245Gln	missense_variant	8/11	ENST00000258455.8	NP_872578.1
MRPS9	XM_011511644.3 linkuse as main transcript	c.362G>A	p.Arg121Gln	missense_variant	7/10		XP_011509946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MRPS9	ENST00000258455.8 linkuse as main transcript	c.734G>A	p.Arg245Gln	missense_variant	8/11	1	NM_182640.3	ENSP00000258455	P1
MRPS9-AS1	ENST00000669390.1 linkuse as main transcript	n.851C>T		non_coding_transcript_exon_variant	7/7
MRPS9	ENST00000472220.1 linkuse as main transcript	n.386G>A		non_coding_transcript_exon_variant	1/4	2
MRPS9	ENST00000413583.5 linkuse as main transcript	c.*150G>A		3_prime_UTR_variant, NMD_transcript_variant	4/6	3		ENSP00000388885

Frequencies

GnomAD3 genomes

AF:

0.00410

AC:

624

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00648

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00604

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00373

AC:

937

AN:

250986

Hom.:

AF XY:

0.00365

AC XY:

495

AN XY:

135656

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00319

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00494

Gnomad NFE exome

AF:

0.00586

Gnomad OTH exome

AF:

0.00556

GnomAD4 exome

AF:

0.00559

AC:

8168

AN:

1461606

Hom.:

Cov.:

AF XY:

0.00542

AC XY:

3944

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.00347

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00507

Gnomad4 NFE exome

AF:

0.00663

Gnomad4 OTH exome

AF:

0.00530

GnomAD4 genome

AF:

0.00410

AC:

625

AN:

152300

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

289

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00647

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00405

Gnomad4 NFE

AF:

0.00604

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00547

Hom.:

Bravo

AF:

0.00421

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00535

AC:

ExAC

AF:

0.00406

AC:

493

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

MRPS9: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Uncertain

0.13

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.087

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.73

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.011

MetaSVM

Uncertain

0.59

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.62

Sift

Benign

0.049

Sift4G

Uncertain

0.060

Polyphen

1.0

Vest4

0.49

MVP

0.99

MPC

0.62

ClinPred

0.023

GERP RS

5.6

Varity_R

0.41

gMVP

0.72

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over