17-75262005-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.171
Variant links:
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]

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ACMG classification

Classification made for transcript

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/exons MANE Protein UniProt
MRPS7NM_015971.4 linkuse as main transcriptc.83+22G>C intron_variant ENST00000245539.11 NP_057055.2
GGA3NM_001172703.3 linkuse as main transcriptc.-177+277C>G intron_variant NP_001166174.1
GGA3NM_001172704.3 linkuse as main transcriptc.-228+277C>G intron_variant NP_001166175.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MRPS7ENST00000245539.11 linkuse as main transcriptc.83+22G>C intron_variant 1 NM_015971.4 ENSP00000245539 P1

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
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 14, 2018This 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201957984; hg19: chr17-73258086; COSMIC: COSV55454041; COSMIC: COSV55454041; API