chr8-73291192-C-T

Variant names:

• chr8-73291192-C-T
• rs1399972665
• NM_000971.4:c.599G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000971.4(RPL7):​c.599G>A​(p.Arg200His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RPL7 NM_000971.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.10
• Publications: 0 publications found

Genes affected

RPL7 (HGNC:10363): (ribosomal protein L7) 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 60S subunit. The protein belongs to the L30P family of ribosomal proteins. It contains an N-terminal basic region-leucine zipper (BZIP)-like domain and the RNP consensus submotif RNP2. In vitro the BZIP-like domain mediates homodimerization and stable binding to DNA and RNA, with a preference for 28S rRNA and mRNA. The protein can inhibit cell-free translation of mRNAs, suggesting that it plays a regulatory role in the translation apparatus. It is located in the cytoplasm. The protein has been shown to be an autoantigen in patients with systemic autoimmune diseases, such as systemic lupus erythematosus. 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058231056).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000971.4. 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
	RPL7	NM_000971.4	MANE Select	c.599G>A	p.Arg200His	missense	Exon 6 of 7	NP_000962.2
	RPL7	NM_001363737.2		c.479G>A	p.Arg160His	missense	Exon 6 of 7	NP_001350666.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL7	ENST00000352983.7	TSL:1 MANE Select	c.599G>A	p.Arg200His	missense	Exon 6 of 7	ENSP00000339795.2
	RPL7	ENST00000863689.1		c.599G>A	p.Arg200His	missense	Exon 6 of 6	ENSP00000533748.1
	RPL7	ENST00000863690.1		c.599G>A	p.Arg200His	missense	Exon 6 of 7	ENSP00000533749.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458104 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 725590

African (AFR) AF: 0.00 AC: 0 AN: 33338

American (AMR) AF: 0.00 AC: 0 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108752

Other (OTH) AF: 0.00 AC: 0 AN: 60250

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.85
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.68	N
PhyloP100		1.1
PrimateAI	Benign	0.42	T
PROVEAN	Benign	2.6	N
REVEL	Benign	0.21
Sift	Benign	0.79	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.034
MutPred		0.43		Loss of MoRF binding (P = 0.0447)
MVP		0.28
MPC		2.1
ClinPred		0.87	D
GERP RS		3.1
Varity_R		0.061
gMVP		0.84
Mutation Taster		=63/37	polymorphism

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: rs1399972665; hg19: chr8-74203427; COSMIC: COSV53583842; COSMIC: COSV53583842;