17-75262003-C-CG

Position:

• chr17-75262003-C-CG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_015971.4(MRPS7):​c.83+22dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000675 in 1,450,236 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (3 hom., cov: 31)
  • Exomes 𝑓: 0.00038 (0 hom.)
• Consequence: MRPS7 NM_015971.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.336

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 -10 ACMG points.

• BP6: Variant 17-75262003-C-CG is Benign according to our data. Variant chr17-75262003-C-CG is described in ClinVar as [Likely_benign]. Clinvar id is 1318189.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (444/38926) while in subpopulation AFR AF= 0.0359 (371/10322). AF 95% confidence interval is 0.0329. There are 3 homozygotes in gnomad4. There are 210 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS7	NM_015971.4	c.83+22dup		intron_variant		ENST00000245539.11	NP_057055.2
GGA3	NM_001172703.3	c.-177+278_-177+279insC		intron_variant			NP_001166174.1
GGA3	NM_001172704.3	c.-228+278_-228+279insC		intron_variant			NP_001166175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS7	ENST00000245539.11	c.83+22dup		intron_variant		1	NM_015971.4	ENSP00000245539	P1

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 443 AN: 38870 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.0360

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00650

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000856

Gnomad OTH AF: 0.00676

GnomAD3 exomes AF: 0.00239 AC: 137 AN: 57250 Hom.: 0 AF XY: 0.00184 AC XY: 59 AN XY: 32022

Gnomad AFR exome AF: 0.0156

Gnomad AMR exome AF: 0.00298

Gnomad ASJ exome AF: 0.0115

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000705

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000445

Gnomad OTH exome AF: 0.00119

GnomAD4 exome AF: 0.000379 AC: 535 AN: 1411310 Hom.: 0 Cov.: 44 AF XY: 0.000388 AC XY: 272 AN XY: 701500

Gnomad4 AFR exome AF: 0.00588

Gnomad4 AMR exome AF: 0.000811

Gnomad4 ASJ exome AF: 0.00613

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000144

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000581

Gnomad4 OTH exome AF: 0.00121

GnomAD4 genome AF: 0.0114 AC: 444 AN: 38926 Hom.: 3 Cov.: 31 AF XY: 0.0115 AC XY: 210 AN XY: 18306

Gnomad4 AFR AF: 0.0359

Gnomad4 AMR AF: 0.00650

Gnomad4 ASJ AF: 0.0205

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000856

Gnomad4 OTH AF: 0.00673

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 23, 2020

- -

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: rs200739528; hg19: chr17-73258084;