17-75262004-GGC-G

Position:

• chr17-75262004-GGC-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_015971.4(MRPS7):​c.83+23_83+24del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 1,557,946 control chromosomes in the GnomAD database, including 544,674 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (49031 hom., cov: 0)
  • Exomes 𝑓: 0.84 (495643 hom.)
• Consequence: MRPS7 NM_015971.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.171

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]

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 17-75262004-GGC-G is Benign according to our data. Variant chr17-75262004-GGC-G is described in ClinVar as [Benign]. Clinvar id is 1263999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS7	NM_015971.4	c.83+23_83+24del		intron_variant		ENST00000245539.11	NP_057055.2
GGA3	NM_001172703.3	c.-177+276_-177+277del		intron_variant			NP_001166174.1
GGA3	NM_001172704.3	c.-228+276_-228+277del		intron_variant			NP_001166175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS7	ENST00000245539.11	c.83+23_83+24del		intron_variant		1	NM_015971.4	ENSP00000245539	P1

Frequencies

GnomAD3 genomes AF: 0.812 AC: 121479 AN: 149518 Hom.: 49009 Cov.: 0

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.761

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.789

GnomAD3 exomes AF: 0.849 AC: 192256 AN: 226428 Hom.: 81125 AF XY: 0.850 AC XY: 106068 AN XY: 124766

Gnomad AFR exome AF: 0.722

Gnomad AMR exome AF: 0.893

Gnomad ASJ exome AF: 0.749

Gnomad EAS exome AF: 0.929

Gnomad SAS exome AF: 0.910

Gnomad FIN exome AF: 0.899

Gnomad NFE exome AF: 0.825

Gnomad OTH exome AF: 0.825

GnomAD4 exome AF: 0.845 AC: 1189657 AN: 1408318 Hom.: 495643 AF XY: 0.846 AC XY: 593846 AN XY: 701570

Gnomad4 AFR exome AF: 0.698

Gnomad4 AMR exome AF: 0.893

Gnomad4 ASJ exome AF: 0.754

Gnomad4 EAS exome AF: 0.943

Gnomad4 SAS exome AF: 0.914

Gnomad4 FIN exome AF: 0.895

Gnomad4 NFE exome AF: 0.839

Gnomad4 OTH exome AF: 0.835

GnomAD4 genome AF: 0.812 AC: 121549 AN: 149628 Hom.: 49031 Cov.: 0 AF XY: 0.819 AC XY: 59944 AN XY: 73164

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.850

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.936

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.901

Gnomad4 NFE AF: 0.827

Gnomad4 OTH AF: 0.790

Alfa AF: 0.815 Hom.: 6190

Bravo AF: 0.790

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

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

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

Other links and lift over

dbSNP: rs36039201; hg19: chr17-73258085;