rs144881278

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000971.4(RPL7):​c.7G>T​(p.Gly3Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,640 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G3R) has been classified as Uncertain significance.

• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1559476).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000971.4. You can select a different transcript below to see updated ACMG 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	NP_000962.2
	RPL7	NM_001363737.2		c.-107+260G>T		intron	N/A	NP_001350666.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL7	ENST00000352983.7	TSL:1 MANE Select	c.7G>T	p.Gly3Cys	missense	Exon 1 of 7	ENSP00000339795.2
	RPL7	ENST00000863689.1		c.7G>T	p.Gly3Cys	missense	Exon 1 of 6	ENSP00000533748.1
	RPL7	ENST00000863690.1		c.7G>T	p.Gly3Cys	missense	Exon 1 of 7	ENSP00000533749.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461640 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727118

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111906

Other (OTH) AF: 0.00 AC: 0 AN: 60384

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000529525), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
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
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		4.8
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.077
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.011	D
Polyphen		0.32	B
Vest4		0.28
MutPred		0.21		Gain of catalytic residue at M1 (P = 2e-04)
MVP		0.35
MPC		0.41
ClinPred		0.90	D
GERP RS		4.4
PromoterAI		-0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.20
Mutation Taster		=280/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs144881278; hg19: chr8-74205841;