rs10793

Variant names:

• chr2-3580862-T-C
• rs10793
• NM_001011.4:c.565T>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001011.4(RPS7):​c.565T>C​(p.Phe189Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPS7 NM_001011.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.93
• Publications: 1 publications found

Genes affected

RPS7 (HGNC:10440): (ribosomal protein S7) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S7E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPS7 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 8

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.945

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS7	NM_001011.4	MANE Select	c.565T>C	p.Phe189Leu	missense	Exon 7 of 7	NP_001002.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS7	ENST00000645674.2	MANE Select	c.565T>C	p.Phe189Leu	missense	Exon 7 of 7	ENSP00000496757.1
	RPS7	ENST00000462576.5	TSL:1	c.565T>C	p.Phe189Leu	missense	Exon 6 of 6	ENSP00000495273.1
	RPS7	ENST00000472966.1	TSL:1	n.500T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1409916 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 704686

African (AFR) AF: 0.00 AC: 0 AN: 32444

American (AMR) AF: 0.00 AC: 0 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25846

East Asian (EAS) AF: 0.00 AC: 0 AN: 39474

South Asian (SAS) AF: 0.00 AC: 0 AN: 85218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50640

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4502

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1068518

Other (OTH) AF: 0.00 AC: 0 AN: 58616

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.44
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.068	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	-0.053	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.5	D
REVEL	Pathogenic	0.78
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.027	D
Polyphen		0.93	P
Vest4		0.92
MutPred		0.84		Loss of sheet (P = 0.1158)
MVP		0.82
MPC		2.3
ClinPred		1.0	D
GERP RS		4.6
Varity_R		0.83
gMVP		0.86
Mutation Taster		=10/90	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: rs10793; hg19: chr2-3628452;