rs115047866

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PS3PP5

The NM_015971.4(MRPS7):c.550A>G(p.Met184Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,614,132 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). ClinVar reports functional evidence for this variant: "SCV000787465: "Well-established functional studies show a deleterious effect (PMID:25556185)."".

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

MRPS7
NM_015971.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:4U:2

Conservation

PhyloP100: 9.32

Publications

10 publications found

Variant links:

Genes affected

MRPS7 (HGNC:14499): (mitochondrial ribosomal protein S7) 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. In the prokaryotic ribosome, the comparable protein is thought to play an essential role in organizing the 3' domain of the 16 S rRNA in the vicinity of the P- and A-sites. Pseudogenes corresponding to this gene are found on chromosomes 8p and 12p. [provided by RefSeq, Jul 2008]

MRPS7 Gene-Disease associations (from GenCC):

syndromic sensorineural deafness due to combined oxidative phosphorylation defect
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
combined oxidative phosphorylation deficiency 34
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

MRPS7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

PS3

PS3 evidence extracted from ClinVar submissions: SCV000787465: "Well-established functional studies show a deleterious effect (PMID:25556185)."

PP5

Variant 17-75265744-A-G is Pathogenic according to our data. Variant chr17-75265744-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 489402.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015971.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS7	NM_015971.4	MANE Select	c.550A>G	p.Met184Val	missense	Exon 5 of 5	NP_057055.2	Q9Y2R9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRPS7	ENST00000245539.11	TSL:1 MANE Select	c.550A>G	p.Met184Val	missense	Exon 5 of 5	ENSP00000245539.6	Q9Y2R9
MRPS7	ENST00000579002.5	TSL:2	c.637A>G	p.Met213Val	missense	Exon 4 of 4	ENSP00000463683.1	J3QLS3
MRPS7	ENST00000886316.1		c.550A>G	p.Met184Val	missense	Exon 5 of 6	ENSP00000556375.1

Frequencies

GnomAD3 genomes

AF:

0.000637

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00118

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000781

AC:

196

AN:

251036

AF XY:

0.000759

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000867

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00127

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00107

AC:

1569

AN:

1461784

Hom.:

Cov.:

AF XY:

0.000993

AC XY:

722

AN XY:

727172

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33480

American (AMR)

AF:

0.000693

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000464

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000150

AC:

AN:

53314

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00130

AC:

1444

AN:

1112010

Other (OTH)

AF:

0.000662

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

101

202

303

404

505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000637

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41574

American (AMR)

AF:

0.000523

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00118

AC:

AN:

68034

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000971

Hom.:

Bravo

AF:

0.000782

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.000807

AC:

EpiCase

AF:

0.000981

EpiControl

AF:

0.00124

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Combined oxidative phosphorylation deficiency 34 (4)

not provided (1)

See cases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.38

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.46

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.5

PhyloP100

9.3

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.1

REVEL

Pathogenic

0.81

Sift

Benign

0.048

Sift4G

Uncertain

0.031

Polyphen

0.92

Vest4

0.92

MVP

0.88

MPC

0.27

ClinPred

0.10

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.54

gMVP

0.74

Mutation Taster

=3/97

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over