NM_000971.4:c.7_9delGGTinsCGA

Variant names:

• chr8-73293604-ACC-TCG
• NM_000971.4:c.7_9delGGTinsCGA
• RPL7 p.Gly3Arg

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-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). PM2

The NM_000971.4(RPL7):c.7_9delGGTinsCGA (p.Gly3Arg) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.G3C: unknown significance (ClinVar VariationId 4348470); p.G3R: Uncertain_significance (ClinVar VariationId 3315219, 1 star)

• Frequency: Genomes: not found (cov: 32)
• 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 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 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.7_9delGGTinsCGA p.Gly3Arg	missense	N/A	Prot: NP_000962.2
	RPL7 NM_001363737.2		c.-107+260_-107+262delGGTinsCGA	intron	Intron 1 of 6	Prot: NP_001350666.1 UniProt:

RPL7 NM_000971.4

MANE Select

HGVSc / HGVSpc.7_9delGGTinsCGAp.Gly3Arg

Exon rankN/A

missense

Prot: NP_000962.2

RPL7 NM_001363737.2

HGVSc / HGVSpc.-107+260_-107+262delGGTinsCGA

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.7_9delGGTinsCGA p.Gly3Arg	missense	N/A	Prot: ENSP00000339795.2 UniProt:
	RPL7 ENST00000863689.1		c.7_9delGGTinsCGA p.Gly3Arg	missense	N/A	Prot: ENSP00000533748.1 UniProt:
	RPL7 ENST00000863690.1		c.7_9delGGTinsCGA p.Gly3Arg	missense	N/A	Prot: ENSP00000533749.1 UniProt:

RPL7 ENST00000352983.7

TSL:1MANE Select

HGVSc / HGVSpc.7_9delGGTinsCGAp.Gly3Arg

Exon rankN/A

missense

Prot: ENSP00000339795.2UniProt: P18124

RPL7 ENST00000863689.1

HGVSc / HGVSpc.7_9delGGTinsCGAp.Gly3Arg

Exon rankN/A

missense

Prot: ENSP00000533748.1UniProt: P18124

RPL7 ENST00000863690.1

HGVSc / HGVSpc.7_9delGGTinsCGAp.Gly3Arg

Exon rankN/A

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 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Uncertain	4.8

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

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

hg19: chr8-74205839;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar