rs144881278

Variant names:

• chr8-73293606-C-A
• rs144881278
• NM_000971.4:c.7G>T
• RPL7 p.Gly3Cys

Your query was ambiguous. Multiple possible variants found:

• chr8-73293606-C-A
• chr8-73293606-C-G
• chr8-73293606-C-T

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

0 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 0 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Moderate

The NM_000971.4(RPL7):c.7G>T (p.Gly3Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant has a gnomAD grpmax filtering allele frequency (95% CI) of 0.00000132, indicating it is observed in the general population. Note: a gnomAD entry for this variant shows a statistical allele-bias signature, consistent with mosaic/somatic contamination (e.g. age-related clonal hematopoiesis) rather than true inherited population frequency — this frequency should not be read as evidence of a common, benign germline variant. 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 (no review stars). Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.G3R: Uncertain_significance (ClinVar VariationId 3315219, 1 star)

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: RPL7 NM_000971.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Very rare in gnomAD for AR/unknown gene (popmax AF < threshold/10) — PM2; GnomAD popmax AF = 0.00000132 — very rare for unknown gene (threshold 0.001) — PM2 moderate.
	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>T p.Gly3Cys	missense	Exon 1 of 7	Prot: NP_000962.2
	RPL7 NM_001363737.2		c.-107+260G>T	intron	Intron 1 of 6	Prot: NP_001350666.1 UniProt:

RPL7 NM_000971.4

MANE Select

HGVSc / HGVSpc.7G>Tp.Gly3Cys

Exon rankExon 1 of 7

missense

Prot: NP_000962.2

RPL7 NM_001363737.2

HGVSc / HGVSpc.-107+260G>T

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>T p.Gly3Cys	missense	Exon 1 of 7	Prot: ENSP00000339795.2 UniProt:
	RPL7 ENST00000863689.1		c.7G>T p.Gly3Cys	missense	Exon 1 of 6	Prot: ENSP00000533748.1 UniProt:
	RPL7 ENST00000863690.1		c.7G>T p.Gly3Cys	missense	Exon 1 of 7	Prot: ENSP00000533749.1 UniProt:

RPL7 ENST00000352983.7

TSL:1MANE Select

HGVSc / HGVSpc.7G>Tp.Gly3Cys

Exon rankExon 1 of 7

missense

Prot: ENSP00000339795.2UniProt: P18124

RPL7 ENST00000863689.1

HGVSc / HGVSpc.7G>Tp.Gly3Cys

Exon rankExon 1 of 6

missense

Prot: ENSP00000533748.1UniProt: P18124

RPL7 ENST00000863690.1

HGVSc / HGVSpc.7G>Tp.Gly3Cys

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 5 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 exome Warning	AF: 0.00000342	AC:5	Hom:0	AN:1461640	Cov:30
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32
TOPMed (Bravo)	AF: 0.00000756	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:0	AN:115348	Cov:
Local & regional cohorts 1 source Population-specific and national genomic databases
ChinaMAP Phase 1	AF: 0.0000985	AC:	Hom:	AN:	Cov:

Showing 6 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
SCHEMA(Schizophrenia)	0.00000973	1	102816	0.00000544	1	183832

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Pathogenic	25
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.016
Eigen_PC	Benign	0.069
FATHMM_MKL	Pathogenic	0.98	D
FuncVEP CTI	Pathogenic	0.46
GPN-Star LLR	N/A	-4.2
GPN-Star score	N/A	4.2
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.65	T
Mutation Taster	N/A	280/20	polymorphism
MutationAssessor	Pathogenic	3.0	M
PhyloP100	Uncertain	4.8
popEVE	Benign	-4.5
PrimateAI	Benign	0.42	T
PromoterAI	N/A	-0.020	Neutral
PROVEAN	Benign	-0.75	N
RBP_binding_hub_radar	N/A	0.0
RBP_regulation_power_radar	N/A	1.7
REVEL	Benign	0.077
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.011	D
Varity_R	N/A	0.29
VESM-3B	Benign	-8.5

Showing 31 of 31 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.020
SpliceAI score (max)	Benign	0.12	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