17-75262005-G-C

Variant names:

• chr17-75262005-G-C
• rs201957984
• NM_015971.4:c.83+22G>C

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+22G>C 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 0.40 (1451 hom., cov: 0)
  • Exomes 𝑓: 0.43 (18518 hom.)
  • Failed GnomAD Quality Control
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 17-75262005-G-C is Benign according to our data. Variant chr17-75262005-G-C is described in ClinVar as [Benign]. Clinvar id is 676153.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+22G>C		intron_variant	Intron 1 of 4	ENST00000245539.11	NP_057055.2
GGA3	NM_001172703.3	c.-177+277C>G		intron_variant	Intron 1 of 16		NP_001166174.1
GGA3	NM_001172704.3	c.-228+277C>G		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+22G>C		intron_variant	Intron 1 of 4	1	NM_015971.4	ENSP00000245539.6

Frequencies

GnomAD3 genomes AF: 0.00 AC: 18997 AN: 47820 Hom.: 1451 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.456

GnomAD3 exomes AF: 0.134 AC: 30698 AN: 228714 Hom.: 2363 AF XY: 0.137 AC XY: 17303 AN XY: 126046

Gnomad AFR exome AF: 0.0408

Gnomad AMR exome AF: 0.0884

Gnomad ASJ exome AF: 0.250

Gnomad EAS exome AF: 0.0655

Gnomad SAS exome AF: 0.0845

Gnomad FIN exome AF: 0.0999

Gnomad NFE exome AF: 0.179

Gnomad OTH exome AF: 0.164

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.433 AC: 224753 AN: 519386 Hom.: 18518 Cov.: 0 AF XY: 0.438 AC XY: 111032 AN XY: 253550

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.453

Gnomad4 ASJ exome AF: 0.540

Gnomad4 EAS exome AF: 0.447

Gnomad4 SAS exome AF: 0.442

Gnomad4 FIN exome AF: 0.502

Gnomad4 NFE exome AF: 0.437

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.397 AC: 19016 AN: 47880 Hom.: 1451 Cov.: 0 AF XY: 0.396 AC XY: 8992 AN XY: 22690

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.453

Alfa AF: 0.149 Hom.: 199

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.1
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201957984; hg19: chr17-73258086; COSMIC: COSV55454041; COSMIC: COSV55454041;