8-73293606-C-G

Variant names:

• chr8-73293606-C-G
• rs144881278
• NM_000971.4:c.7G>C
• RPL7 p.Gly3Arg

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-2 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.77
• 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]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

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

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		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	Prot: NP_000962.2
	RPL7 NM_001363737.2		c.-107+260G>C	intron	Intron 1 of 6	Prot: NP_001350666.1 UniProt:

RPL7 NM_000971.4

MANE Select

HGVSc / HGVSpc.7G>Cp.Gly3Arg

Exon rankExon 1 of 7

missense

Prot: NP_000962.2

RPL7 NM_001363737.2

HGVSc / HGVSpc.-107+260G>C

Exon rankIntron 1 of 6

intron

Prot: NP_001350666.1UniProt: A8MUD9

Ensembl Transcripts

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

RPL7 ENST00000352983.7

TSL:1MANE Select

HGVSc / HGVSpc.7G>Cp.Gly3Arg

Exon rankExon 1 of 7

missense

Prot: ENSP00000339795.2UniProt: P18124

RPL7 ENST00000863689.1

HGVSc / HGVSpc.7G>Cp.Gly3Arg

Exon rankExon 1 of 6

missense

Prot: ENSP00000533748.1UniProt: P18124

RPL7 ENST00000863690.1

HGVSc / HGVSpc.7G>Cp.Gly3Arg

Exon rankExon 1 of 7

missense

Prot: ENSP00000533749.1UniProt: 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	AF: 0.000427	AC:65	Hom:0	AN:152168	Cov:32
GnomAD2 exomes	AF: 0.0000916	AC:23	Hom:	AN:251030	Cov:
GnomAD4 exome	AF: 0.0000397	AC:58	Hom:0	AN:1461640	Cov:30
GnomAD4 genome	AF: 0.000427	AC:65	Hom:0	AN:152286	Cov:32
TOPMed (Bravo)	AF: 0.000446	AC:118	Hom:0	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.0000867	AC:10	Hom:0	AN:115348	Cov:
Local & regional cohorts 3 sources Population-specific and national genomic databases
ChinaMAP Phase 1	AF: 0.0000985	AC:	Hom:	AN:	Cov:
ESP6500 (Exome Variant Server)	AF: 0.000538	AC:7	Hom:	AN:13006	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.000223	AC:2	Hom:0	AN:8960	Cov:

Showing 9 sources

Case/control cohorts

Cohort	Cases			Controls
	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

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

Computational Scores

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

Showing 31 of 31 scores

Splicing Scores

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

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.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs144881278;

hg19: chr8-74205841;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar