17-75262006-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 676154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015971.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS7	NM_015971.4	MANE Select	c.83+23C>G		intron	N/A	NP_057055.2	Q9Y2R9
	GGA3	NM_001172703.3		c.-177+276G>C		intron	N/A	NP_001166174.1	Q9NZ52-4
	GGA3	NM_001172704.3		c.-228+276G>C		intron	N/A	NP_001166175.1	Q9NZ52-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS7	ENST00000245539.11	TSL:1 MANE Select	c.83+23C>G		intron	N/A	ENSP00000245539.6	Q9Y2R9
	MRPS7	ENST00000579002.5	TSL:2	c.-321C>G		5_prime_UTR	Exon 1 of 4	ENSP00000463683.1	J3QLS3
	GGA3	ENST00000582717.5	TSL:2	c.-177+276G>C		intron	N/A	ENSP00000462081.1	Q9NZ52-4

Frequencies

GnomAD3 genomes AF: 0.520 AC: 19769 AN: 38010 Hom.: 1503 Cov.: 0

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

GnomAD2 exomes AF: 0.136 AC: 31175 AN: 228750 AF XY: 0.139

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 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

African (AFR) AF: 0.336 AC: 2012 AN: 5992

American (AMR) AF: 0.525 AC: 4053 AN: 7726

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 6726 AN: 11746

East Asian (EAS) AF: 0.514 AC: 2166 AN: 4218

South Asian (SAS) AF: 0.523 AC: 7334 AN: 14028

European-Finnish (FIN) AF: 0.530 AC: 4320 AN: 8152

Middle Eastern (MID) AF: 0.587 AC: 1512 AN: 2578

European-Non Finnish (NFE) AF: 0.539 AC: 189273 AN: 350936

Other (OTH) AF: 0.535 AC: 9290 AN: 17368

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

African (AFR) AF: 0.406 AC: 2656 AN: 6540

American (AMR) AF: 0.527 AC: 1926 AN: 3654

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 931 AN: 1588

East Asian (EAS) AF: 0.510 AC: 320 AN: 628

South Asian (SAS) AF: 0.521 AC: 405 AN: 778

European-Finnish (FIN) AF: 0.520 AC: 1068 AN: 2054

Middle Eastern (MID) AF: 0.571 AC: 72 AN: 126

European-Non Finnish (NFE) AF: 0.548 AC: 11920 AN: 21760

Other (OTH) AF: 0.535 AC: 348 AN: 650

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Combined oxidative phosphorylation deficiency 34 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.9
DANN	Benign	0.40
PhyloP100		0.0
PromoterAI		-0.025	Neutral
Mutation Taster		=145/155	disease causing

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

Other links and lift over

dbSNP: rs62085969; hg19: chr17-73258087;