17-75261947-C-T

Position:

chr17-75261947-C-T

Variant summary

Our verdict is Benign. Variant got -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. 14/21 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

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 made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 380587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MRPS7	NM_015971.4 linkuse as main transcript	c.47C>T	p.Ala16Val	missense_variant	1/5	ENST00000245539.11	NP_057055.2
GGA3	NM_001172703.3 linkuse as main transcript	c.-177+335G>A		intron_variant			NP_001166174.1
GGA3	NM_001172704.3 linkuse as main transcript	c.-228+335G>A		intron_variant			NP_001166175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS7	ENST00000245539.11 linkuse as main transcript	c.47C>T	p.Ala16Val	missense_variant	1/5	1	NM_015971.4	ENSP00000245539	P1

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

GnomAD3 exomes

AF:

0.00436

AC:

1056

AN:

242322

Hom.:

AF XY:

0.00431

AC XY:

571

AN XY:

132346

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 SAS exome

AF:

0.00160

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

Gnomad4 AFR exome

AF:

0.000957

Gnomad4 AMR exome

AF:

0.00291

Gnomad4 ASJ exome

AF:

0.0104

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00177

Gnomad4 FIN exome

AF:

0.00106

Gnomad4 NFE exome

AF:

0.00737

Gnomad4 OTH exome

AF:

0.00726

GnomAD4 genome

AF:

0.00415

AC:

632

AN:

152192

Hom.:

Cov.:

AF XY:

0.00371

AC XY:

276

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.00688

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00628

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

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 05, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	GGA3: BS2; MRPS7: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.0

DANN

Uncertain

0.98

DEOGEN2

Benign

0.083

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.0044

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

.;L

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.1

.;N

REVEL

Benign

0.012

Sift

Benign

0.093

.;T

Sift4G

Benign

0.11

T;T

Polyphen

0.0010

.;B

Vest4

0.074

MVP

0.39

MPC

0.11

ClinPred

0.0029

GERP RS

-4.2

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Varity_R

0.046

gMVP

0.20

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

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