17-75261947-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015971.4(MRPS7):c.47C>T(p.Ala16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 1,608,276 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 3 hom., cov: 34)

Exomes 𝑓: 0.0064 ( 47 hom. )

Consequence

MRPS7
NM_015971.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.55

Publications

6 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 links:

GGA3 (HGNC:17079): (golgi associated, gamma adaptin ear containing, ARF binding protein 3) This gene encodes a member of the Golgi-localized, gamma adaptin ear-containing, ARF-binding (GGA) family. This family includes ubiquitous coat proteins that regulate the trafficking of proteins between the trans-Golgi network and the lysosome. These proteins share an amino-terminal VHS domain which mediates sorting of the mannose 6-phosphate receptors at the trans-Golgi network. They also contain a carboxy-terminal region with homology to the ear domain of gamma-adaptins. Multiple alternatively spliced transcript variants have been identified in this gene. [provided by RefSeq, Feb 2010]

GGA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004424423).

BP6

Variant 17-75261947-C-T is Benign according to our data. Variant chr17-75261947-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 380587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR,Unknown gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRPS7	NM_015971.4	MANE Select	c.47C>T	p.Ala16Val	missense	Exon 1 of 5	NP_057055.2	Q9Y2R9
GGA3	NM_001172703.3		c.-177+335G>A		intron	N/A	NP_001166174.1	Q9NZ52-4
GGA3	NM_001172704.3		c.-228+335G>A		intron	N/A	NP_001166175.1	Q9NZ52-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRPS7	ENST00000245539.11	TSL:1 MANE Select	c.47C>T	p.Ala16Val	missense	Exon 1 of 5	ENSP00000245539.6	Q9Y2R9
MRPS7	ENST00000886316.1		c.47C>T	p.Ala16Val	missense	Exon 1 of 6	ENSP00000556375.1
MRPS7	ENST00000912532.1		c.47C>T	p.Ala16Val	missense	Exon 1 of 6	ENSP00000582591.1

Frequencies

GnomAD3 genomes

AF:

0.00415

AC:

631

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00687

Gnomad OTH

AF:

0.00384

GnomAD2 exomes

AF:

0.00436

AC:

1056

AN:

242322

AF XY:

0.00431

show subpopulations

Gnomad AFR exome

AF:

0.00108

Gnomad AMR exome

AF:

0.00255

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00112

Gnomad NFE exome

AF:

0.00675

Gnomad OTH exome

AF:

0.00647

GnomAD4 exome

AF:

0.00640

AC:

9315

AN:

1456084

Hom.:

Cov.:

AF XY:

0.00629

AC XY:

4556

AN XY:

724732

show subpopulations

African (AFR)

AF:

0.000957

AC:

AN:

33452

American (AMR)

AF:

0.00291

AC:

130

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

272

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00177

AC:

153

AN:

86246

European-Finnish (FIN)

AF:

0.00106

AC:

AN:

47956

Middle Eastern (MID)

AF:

0.00867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00737

AC:

8189

AN:

1111842

Other (OTH)

AF:

0.00726

AC:

438

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

508

1015

1523

2030

2538

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

318

636

954

1272

1590

<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:

0.00415

AC:

632

AN:

152192

Hom.:

Cov.:

AF XY:

0.00371

AC XY:

276

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

41514

American (AMR)

AF:

0.00307

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00145

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00170

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00688

AC:

468

AN:

68014

Other (OTH)

AF:

0.00380

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

100

134

167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00594

Hom.:

Bravo

AF:

0.00426

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00675

AC:

ExAC

AF:

0.00403

AC:

488

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00921

EpiControl

AF:

0.00806

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.0

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.083

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.57

M_CAP

Benign

0.0044

MetaRNN

Benign

0.0044

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

-2.6

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.1

REVEL

Benign

0.012

Sift

Benign

0.093

Sift4G

Benign

0.11

Polyphen

0.0010

Vest4

0.074

MVP

0.39

MPC

0.11

ClinPred

0.0029

GERP RS

-4.2

PromoterAI

0.0052

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Varity_R

0.046

gMVP

0.20

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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