17-75262006-C-G

Variant names:

• chr17-75262006-C-G
• rs62085969
• NM_015971.4:c.83+23C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_015971.4(MRPS7):​c.83+23C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (1504 hom., cov: 0)
  • Exomes 𝑓: 0.54 (19045 hom.)
  • Failed GnomAD Quality Control
• Consequence: MRPS7 NM_015971.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.00

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 17-75262006-C-G is Benign according to our data. Variant chr17-75262006-C-G is described in ClinVar as [Benign]. Clinvar id is 676154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS7	NM_015971.4	c.83+23C>G		intron_variant	Intron 1 of 4	ENST00000245539.11	NP_057055.2
GGA3	NM_001172703.3	c.-177+276G>C		intron_variant	Intron 1 of 16		NP_001166174.1
GGA3	NM_001172704.3	c.-228+276G>C		intron_variant	Intron 1 of 15		NP_001166175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS7	ENST00000245539.11	c.83+23C>G		intron_variant	Intron 1 of 4	1	NM_015971.4	ENSP00000245539.6

Frequencies

GnomAD3 genomes AF: 0.00 AC: 19769 AN: 38010 Hom.: 1503 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.535

GnomAD3 exomes AF: 0.136 AC: 31175 AN: 228750 Hom.: 2467 AF XY: 0.139 AC XY: 17514 AN XY: 126062

Gnomad AFR exome AF: 0.0552

Gnomad AMR exome AF: 0.0900

Gnomad ASJ exome AF: 0.259

Gnomad EAS exome AF: 0.0653

Gnomad SAS exome AF: 0.0850

Gnomad FIN exome AF: 0.0996

Gnomad NFE exome AF: 0.180

Gnomad OTH exome AF: 0.166

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.536 AC: 226686 AN: 422744 Hom.: 19045 Cov.: 0 AF XY: 0.537 AC XY: 111976 AN XY: 208486

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.525

Gnomad4 ASJ exome AF: 0.573

Gnomad4 EAS exome AF: 0.514

Gnomad4 SAS exome AF: 0.523

Gnomad4 FIN exome AF: 0.530

Gnomad4 NFE exome AF: 0.539

Gnomad4 OTH exome AF: 0.535

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.520 AC: 19790 AN: 38054 Hom.: 1504 Cov.: 0 AF XY: 0.518 AC XY: 9346 AN XY: 18044

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.535

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Combined oxidative phosphorylation deficiency 34 Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.9
DANN	Benign	0.40

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: rs62085969; hg19: chr17-73258087;