chr17-75262005-GC-G

Variant names:

• chr17-75262005-GC-G
• rs10539706
• NM_015971.4:c.83+23delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015971.4(MRPS7):​c.83+23delC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (559 hom., cov: 0)
  • Exomes 𝑓: 0.017 (475 hom.)
• Consequence: MRPS7 NM_015971.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00
• Publications: 1 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 -10 ACMG points.

• BP6: Variant 17-75262005-GC-G is Benign according to our data. Variant chr17-75262005-GC-G is described in ClinVar as Benign. ClinVar VariationId is 1231509.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

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+23delC		intron	N/A	NP_057055.2	Q9Y2R9
	GGA3	NM_001172703.3		c.-177+276delG		intron	N/A	NP_001166174.1	Q9NZ52-4
	GGA3	NM_001172704.3		c.-228+276delG		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+23delC		intron	N/A	ENSP00000245539.6	Q9Y2R9
	MRPS7	ENST00000579002.5	TSL:2	c.-321delC		5_prime_UTR	Exon 1 of 4	ENSP00000463683.1	J3QLS3
	GGA3	ENST00000582717.5	TSL:2	c.-177+276delG		intron	N/A	ENSP00000462081.1	Q9NZ52-4

Frequencies

GnomAD3 genomes AF: 0.149 AC: 7112 AN: 47848 Hom.: 554 Cov.: 0

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0692

Gnomad ASJ AF: 0.00831

Gnomad EAS AF: 0.0168

Gnomad SAS AF: 0.0162

Gnomad FIN AF: 0.00194

Gnomad MID AF: 0.0294

Gnomad NFE AF: 0.00543

Gnomad OTH AF: 0.0963

GnomAD2 exomes AF: 0.0132 AC: 3021 AN: 228714 AF XY: 0.0105

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.0115

Gnomad ASJ exome AF: 0.00395

Gnomad EAS exome AF: 0.00187

Gnomad FIN exome AF: 0.000891

Gnomad NFE exome AF: 0.00160

Gnomad OTH exome AF: 0.00813

GnomAD4 exome AF: 0.0171 AC: 8825 AN: 517564 Hom.: 475 Cov.: 0 AF XY: 0.0155 AC XY: 3906 AN XY: 252656

African (AFR) AF: 0.402 AC: 5488 AN: 13660

American (AMR) AF: 0.0638 AC: 557 AN: 8726

Ashkenazi Jewish (ASJ) AF: 0.00953 AC: 114 AN: 11964

East Asian (EAS) AF: 0.0129 AC: 62 AN: 4810

South Asian (SAS) AF: 0.0126 AC: 207 AN: 16370

European-Finnish (FIN) AF: 0.0141 AC: 119 AN: 8410

Middle Eastern (MID) AF: 0.0192 AC: 53 AN: 2762

European-Non Finnish (NFE) AF: 0.00325 AC: 1398 AN: 429700

Other (OTH) AF: 0.0391 AC: 827 AN: 21162

GnomAD4 genome AF: 0.149 AC: 7133 AN: 47908 Hom.: 559 Cov.: 0 AF XY: 0.148 AC XY: 3357 AN XY: 22712

African (AFR) AF: 0.422 AC: 6614 AN: 15674

American (AMR) AF: 0.0692 AC: 281 AN: 4060

Ashkenazi Jewish (ASJ) AF: 0.00831 AC: 13 AN: 1564

East Asian (EAS) AF: 0.0154 AC: 10 AN: 650

South Asian (SAS) AF: 0.0162 AC: 13 AN: 802

European-Finnish (FIN) AF: 0.00194 AC: 4 AN: 2064

Middle Eastern (MID) AF: 0.0299 AC: 4 AN: 134

European-Non Finnish (NFE) AF: 0.00543 AC: 119 AN: 21930

Other (OTH) AF: 0.0995 AC: 75 AN: 754

Alfa AF: 0.00221 Hom.: 1

Bravo AF: 0.0545

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=300/0	polymorphism (auto)

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: rs10539706; hg19: chr17-73258086;