8-73293606-C-G

Variant names:

Variant summary

Our verdict is The variant received -2 classification points (ACMG Germline Pathogenicity v2019). BP4_Moderate

The NM_000971.4(RPL7):c.7G>C (p.Gly3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.0000762 (AC=123) in the gnomAD database across 1,613,926 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.00124. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (★). Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.G3C: unknown significance (ClinVar VariationId 4348470)

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

RPL7
NM_000971.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.77

Publications

0 publications found

Variant links:

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]

RPL7 links:

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new If you want to explore the variant's impact on the transcript NM_000971.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Moderate).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000971.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL7	NM_000971.4	MANE Select	c.7G>C	p.Gly3Arg	missense	Exon 1 of 7	NP_000962.2
	RPL7	NM_001363737.2		c.-107+260G>C		intron	N/A	NP_001350666.1	A8MUD9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL7	ENST00000352983.7	TSL:1 MANE Select	c.7G>C	p.Gly3Arg	missense	Exon 1 of 7	ENSP00000339795.2	P18124
RPL7	ENST00000863689.1		c.7G>C	p.Gly3Arg	missense	Exon 1 of 6	ENSP00000533748.1	P18124
RPL7	ENST00000863690.1		c.7G>C	p.Gly3Arg	missense	Exon 1 of 7	ENSP00000533749.1	P18124

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	0.000427	65	0	152168	32
GnomAD2 exomes	0.0000916	23		251030
GnomAD4 exome	0.0000397	58	0	1461640	30
GnomAD4 genome	0.000427	65	0	152286	32
TOPMed (Bravo)	0.000446	118	0	264690
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	0.0000867	10	0	115348
Local & regional cohorts 3 sources Population-specific and national genomic databases
ChinaMAP Phase 1	0.0000985
ESP6500 (Exome Variant Server)	0.000538	7		13006
WBBC (Westlake BioBank for Chinese) pilot	0.000223	2	0	8960

Showing 9 sources

Case/control cohorts

Cohort	Cases			Controls
Cohort	AF	AC	AN	AF	AC	AN
Epi25 (Epilepsy)	0.0000477	2	41958	0.000135	9	66874
SCHEMA (Schizophrenia)	0.000181	22	121372	0.000179	34	189874

Showing 2 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
AlphaGenome AVI	Pathogenic	-	24
AlphaMissense	Benign	-	0.22
BayesDel_addAF	Benign	T	-0.20
BayesDel_noAF	Uncertain	-	-0.070
CADD	Uncertain	-	24
DANN	Uncertain	-	1.0
DEOGEN2	Benign	T	0.14
Eigen	Benign	-	-0.088
Eigen_PC	Benign	-	-0.0044
FATHMM_MKL	Pathogenic	D	0.98
FuncVEP CTI	Benign	-	0.0030
GPN-Star LLR	N/A	-	-3.7
GPN-Star score	N/A	-	3.7
LIST_S2	Benign	T	0.84
M_CAP	Benign	D	0.032
MetaRNN	Benign	T	0.017
MetaSVM	Benign	T	-0.70
Mutation Taster	N/A	polymorphism	79/21
MutationAssessor	Pathogenic	M	3.0
PhyloP100	Uncertain	-	4.8
popEVE	Benign	-	-3.6
PrimateAI	Benign	T	0.44
PromoterAI	N/A	Neutral	0.12
PROVEAN	Benign	N	-0.72
RBP_binding_hub_radar	N/A	-	0.0
RBP_regulation_power_radar	N/A	-	1.7
REVEL	Benign	-	0.051
Sift	Uncertain	D	0.0010
Sift4G	Uncertain	D	0.026
Varity_R	N/A	-	0.17
VESM-3B	Benign	-	-6.4

Showing 31 of 31 scores

Splicing Scores

Algorithm	Calibrated prediction	Prediction	Score
Pangolin (max)	Benign	-	0.0
SpliceAI score (max)	Benign	- Details are displayed if max score is > 0.2	0.0

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Case/control cohorts

ClinVar

Computational Scores

Splicing Scores

Publications

Other links and lift over