17-75261732-G-T

Position:

• chr17-75261732-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000579761.5(MRPS7):​c.-169G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 1,146,000 control chromosomes in the GnomAD database, including 4,811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (2804 hom., cov: 33)
  • Exomes 𝑓: 0.020 (2007 hom.)
• Consequence: MRPS7 ENST00000579761.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.34

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 17-75261732-G-T is Benign according to our data. Variant chr17-75261732-G-T is described in ClinVar as [Benign]. Clinvar id is 1227959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGA3	NM_001172703.3	c.-177+550C>A		intron_variant			NP_001166174.1
GGA3	NM_001172704.3	c.-228+550C>A		intron_variant			NP_001166175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS7	ENST00000579761.5	c.-169G>T		5_prime_UTR_variant	1/4	2		ENSP00000463263
GGA3	ENST00000578348.5	c.-228+550C>A		intron_variant		2		ENSP00000463288
GGA3	ENST00000579743.2	c.-346+550C>A		intron_variant		4		ENSP00000481953

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17295 AN: 152132 Hom.: 2798 Cov.: 33

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0911

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.0768

Gnomad SAS AF: 0.0861

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.00272

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.0197 AC: 19578 AN: 993750 Hom.: 2007 Cov.: 13 AF XY: 0.0207 AC XY: 10182 AN XY: 492124

Gnomad4 AFR exome AF: 0.364

Gnomad4 AMR exome AF: 0.0679

Gnomad4 ASJ exome AF: 0.00882

Gnomad4 EAS exome AF: 0.0609

Gnomad4 SAS exome AF: 0.0769

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00182

Gnomad4 OTH exome AF: 0.0393

GnomAD4 genome AF: 0.114 AC: 17330 AN: 152250 Hom.: 2804 Cov.: 33 AF XY: 0.112 AC XY: 8355 AN XY: 74450

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.0909

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.0770

Gnomad4 SAS AF: 0.0853

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00273

Gnomad4 OTH AF: 0.103

Alfa AF: 0.00780 Hom.: 29

Bravo AF: 0.130

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.1
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs16967742; hg19: chr17-73257813;