17-75261905-C-T

Variant names:

• chr17-75261905-C-T
• rs8075276
• NM_015971.4:c.5C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015971.4(MRPS7):​c.5C>T​(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 1,608,006 control chromosomes in the GnomAD database, including 529,496 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (39343 hom., cov: 33)
  • Exomes 𝑓: 0.82 (490153 hom.)
• Consequence: MRPS7 NM_015971.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.69
• Publications: 37 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.624923E-7).
• BP6: Variant 17-75261905-C-T is Benign according to our data. Variant chr17-75261905-C-T is described in ClinVar as Benign. ClinVar VariationId is 379995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.837 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.5C>T	p.Ala2Val	missense	Exon 1 of 5	NP_057055.2	Q9Y2R9
	GGA3	NM_001172703.3		c.-177+377G>A		intron	N/A	NP_001166174.1	Q9NZ52-4
	GGA3	NM_001172704.3		c.-228+377G>A		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.5C>T	p.Ala2Val	missense	Exon 1 of 5	ENSP00000245539.6	Q9Y2R9
	MRPS7	ENST00000886316.1		c.5C>T	p.Ala2Val	missense	Exon 1 of 6	ENSP00000556375.1
	MRPS7	ENST00000912532.1		c.5C>T	p.Ala2Val	missense	Exon 1 of 6	ENSP00000582591.1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104124 AN: 152018 Hom.: 39333 Cov.: 33

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.899

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.680

GnomAD2 exomes AF: 0.797 AC: 192746 AN: 241700 AF XY: 0.805

Gnomad AFR exome AF: 0.331

Gnomad AMR exome AF: 0.839

Gnomad ASJ exome AF: 0.734

Gnomad EAS exome AF: 0.863

Gnomad FIN exome AF: 0.898

Gnomad NFE exome AF: 0.818

Gnomad OTH exome AF: 0.795

GnomAD4 exome AF: 0.816 AC: 1188012 AN: 1455870 Hom.: 490153 Cov.: 55 AF XY: 0.818 AC XY: 592526 AN XY: 724552

African (AFR) AF: 0.312 AC: 10427 AN: 33464

American (AMR) AF: 0.831 AC: 37057 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 19055 AN: 26048

East Asian (EAS) AF: 0.883 AC: 35022 AN: 39660

South Asian (SAS) AF: 0.836 AC: 72027 AN: 86142

European-Finnish (FIN) AF: 0.898 AC: 43560 AN: 48516

Middle Eastern (MID) AF: 0.687 AC: 3962 AN: 5768

European-Non Finnish (NFE) AF: 0.827 AC: 919389 AN: 1111436

Other (OTH) AF: 0.788 AC: 47513 AN: 60268

GnomAD4 genome AF: 0.685 AC: 104157 AN: 152136 Hom.: 39343 Cov.: 33 AF XY: 0.693 AC XY: 51567 AN XY: 74390

African (AFR) AF: 0.335 AC: 13875 AN: 41444

American (AMR) AF: 0.757 AC: 11572 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2505 AN: 3470

East Asian (EAS) AF: 0.858 AC: 4419 AN: 5152

South Asian (SAS) AF: 0.830 AC: 4010 AN: 4832

European-Finnish (FIN) AF: 0.899 AC: 9536 AN: 10610

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.821 AC: 55829 AN: 68016

Other (OTH) AF: 0.683 AC: 1442 AN: 2112

Alfa AF: 0.785 Hom.: 92019

Bravo AF: 0.661

TwinsUK AF: 0.826 AC: 3064

ALSPAC AF: 0.831 AC: 3203

ESP6500AA AF: 0.359 AC: 1578

ESP6500EA AF: 0.814 AC: 7000

ExAC AF: 0.786 AC: 95081

Asia WGS AF: 0.783 AC: 2725 AN: 3478

EpiCase AF: 0.806

EpiControl AF: 0.805

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)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.41
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.022
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	9.6e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.7
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.083
Sift	Benign	0.052	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.029	B
Vest4		0.19
MPC		0.53
ClinPred		0.057	T
GERP RS		4.8
PromoterAI		-0.58	Under-expression
Varity_R		0.26
gMVP		0.67
Mutation Taster		=98/2	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: rs8075276; hg19: chr17-73257986; COSMIC: COSV55452937; COSMIC: COSV55452937;