chr8-73293606-C-T

Variant names:

• chr8-73293606-C-T
• rs144881278
• NM_000971.4:c.7G>A
• RPL7 p.Gly3Ser

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>A (p.Gly3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.0000353 (AC=57) in the gnomAD database across 1,613,806 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.0000458. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. 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: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000036 (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 = 0.0000458 — 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>A p.Gly3Ser	missense	Exon 1 of 7	Prot: NP_000962.2
	RPL7 NM_001363737.2		c.-107+260G>A	intron	Intron 1 of 6	Prot: NP_001350666.1 UniProt:

RPL7 NM_000971.4

MANE Select

HGVSc / HGVSpc.7G>Ap.Gly3Ser

Exon rankExon 1 of 7

missense

Prot: NP_000962.2

RPL7 NM_001363737.2

HGVSc / HGVSpc.-107+260G>A

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>A p.Gly3Ser	missense	Exon 1 of 7	Prot: ENSP00000339795.2 UniProt:
	RPL7 ENST00000863689.1		c.7G>A p.Gly3Ser	missense	Exon 1 of 6	Prot: ENSP00000533748.1 UniProt:
	RPL7 ENST00000863690.1		c.7G>A p.Gly3Ser	missense	Exon 1 of 7	Prot: ENSP00000533749.1 UniProt:

RPL7 ENST00000352983.7

TSL:1MANE Select

HGVSc / HGVSpc.7G>Ap.Gly3Ser

Exon rankExon 1 of 7

missense

Prot: ENSP00000339795.2UniProt: P18124

RPL7 ENST00000863689.1

HGVSc / HGVSpc.7G>Ap.Gly3Ser

Exon rankExon 1 of 6

missense

Prot: ENSP00000533748.1UniProt: P18124

RPL7 ENST00000863690.1

HGVSc / HGVSpc.7G>Ap.Gly3Ser

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: 0.0000329	AC:5	Hom:0	AN:152168	Cov:32
GnomAD2 exomes	AF: 0.0000438	AC:11	Hom:	AN:251030	Cov:
GnomAD4 exome	AF: 0.0000356	AC:52	Hom:0	AN:1461638	Cov:30
GnomAD4 genome	AF: 0.0000329	AC:5	Hom:0	AN:152168	Cov:32
TOPMed (Bravo)	AF: 0.0000189	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00000867	AC:1	Hom:0	AN:115348	Cov:
Local & regional cohorts 3 sources Population-specific and national genomic databases
GenomeAsia100K	AF: 0.000289	AC:1	Hom:	AN:3478	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.0000160	AC:2	Hom:0	AN:122786	Cov:
Turkish Variome	AF: 0.000178	AC:1	Hom:0	AN:5158	Cov:

Showing 9 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
ASC(Autism)	0.000676 *	1	1480	0.00 *	0	7186
BipEx(Bipolar disorder (including schizoaffective))	0.0000352	1	28420	0.0000693	2	28844
Epi25(Epilepsy)	0.0000477	2	41958	0.0000150	1	66874
SCHEMA(Schizophrenia)	0.0000494	6	121372	0.0000527	10	189876

Showing 4 cohortsAllele 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	23
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.050
FATHMM_MKL	Pathogenic	0.98	D
FuncVEP CTI	Benign	0.0098
GPN-Star LLR	N/A	-3.0
GPN-Star score	N/A	3.0
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.80	T
Mutation Taster	N/A	280/20	polymorphism
MutationAssessor	Benign	1.9	L
PhyloP100	Uncertain	4.8
popEVE	Benign	-2.9
PrimateAI	Benign	0.37	T
PromoterAI	N/A	-0.077	Neutral
PROVEAN	Benign	-0.29	N
RBP_binding_hub_radar	N/A	0.0
RBP_regulation_power_radar	N/A	1.7
REVEL	Benign	0.039
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.17	T
Varity_R	N/A	0.16
VESM-3B	Benign	-4.4

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