17-75261905-C-T

Position:

chr17-75261905-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015971.4(MRPS7):c.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 1,608,006 control chromosomes in the GnomAD database, including 529,496 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 39343 hom., cov: 33)

Exomes 𝑓: 0.82 ( 490153 hom. )

Consequence

MRPS7
NM_015971.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.69

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.624923E-7).

BP6

Variant 17-75261905-C-T is Benign according to our data. Variant chr17-75261905-C-T is described in ClinVar as [Benign]. Clinvar id is 379995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MRPS7	NM_015971.4 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	1/5	ENST00000245539.11	NP_057055.2
GGA3	NM_001172703.3 linkuse as main transcript	c.-177+377G>A		intron_variant			NP_001166174.1
GGA3	NM_001172704.3 linkuse as main transcript	c.-228+377G>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.5C>T	p.Ala2Val	missense_variant	1/5	1	NM_015971.4	ENSP00000245539	P1

Frequencies

GnomAD3 genomes

AF:

0.685

AC:

104124

AN:

152018

Hom.:

39333

Cov.:

show subpopulations

Gnomad AFR

AF:

0.335

Gnomad AMI

AF:

0.842

Gnomad AMR

AF:

0.756

Gnomad ASJ

AF:

0.722

Gnomad EAS

AF:

0.858

Gnomad SAS

AF:

0.829

Gnomad FIN

AF:

0.899

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.821

Gnomad OTH

AF:

0.680

GnomAD3 exomes

AF:

0.797

AC:

192746

AN:

241700

Hom.:

78763

AF XY:

0.805

AC XY:

106190

AN XY:

131982

show subpopulations

Gnomad AFR exome

AF:

0.331

Gnomad AMR exome

AF:

0.839

Gnomad ASJ exome

AF:

0.734

Gnomad EAS exome

AF:

0.863

Gnomad SAS exome

AF:

0.835

Gnomad FIN exome

AF:

0.898

Gnomad NFE exome

AF:

0.818

Gnomad OTH exome

AF:

0.795

GnomAD4 exome

AF:

0.816

AC:

1188012

AN:

1455870

Hom.:

490153

Cov.:

AF XY:

0.818

AC XY:

592526

AN XY:

724552

show subpopulations

Gnomad4 AFR exome

AF:

0.312

Gnomad4 AMR exome

AF:

0.831

Gnomad4 ASJ exome

AF:

0.732

Gnomad4 EAS exome

AF:

0.883

Gnomad4 SAS exome

AF:

0.836

Gnomad4 FIN exome

AF:

0.898

Gnomad4 NFE exome

AF:

0.827

Gnomad4 OTH exome

AF:

0.788

GnomAD4 genome

AF:

0.685

AC:

104157

AN:

152136

Hom.:

39343

Cov.:

AF XY:

0.693

AC XY:

51567

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.335

Gnomad4 AMR

AF:

0.757

Gnomad4 ASJ

AF:

0.722

Gnomad4 EAS

AF:

0.858

Gnomad4 SAS

AF:

0.830

Gnomad4 FIN

AF:

0.899

Gnomad4 NFE

AF:

0.821

Gnomad4 OTH

AF:

0.683

Alfa

AF:

0.793

Hom.:

69121

Bravo

AF:

0.661

TwinsUK

AF:

0.826

AC:

3064

ALSPAC

AF:

0.831

AC:

3203

ESP6500AA

AF:

0.359

AC:

1578

ESP6500EA

AF:

0.814

AC:

7000

ExAC

AF:

0.786

AC:

95081

Asia WGS

AF:

0.783

AC:

2725

AN:

3478

EpiCase

AF:

0.806

EpiControl

AF:

0.805

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 02, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Combined oxidative phosphorylation deficiency 34

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

.;T

Eigen

Benign

-0.022

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.58

T;T

MetaRNN

Benign

9.6e-7

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

.;M

MutationTaster

Benign

2.8e-19

P;P;P;P;P

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.6

.;N

REVEL

Benign

0.083

Sift

Benign

0.052

.;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.029

.;B

Vest4

0.19

MPC

0.53

ClinPred

0.057

GERP RS

4.8

Varity_R

0.26

gMVP

0.67

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