9-133351063-T-A

Position:

• chr9-133351063-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000972.3(RPL7A):​c.688T>A​(p.Tyr230Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPL7A NM_000972.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.60

Genes affected

RPL7A (HGNC:10364): (ribosomal protein L7a) Cytoplasmic ribosomes, 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 L7AE family of ribosomal proteins. It can interact with a subclass of nuclear hormone receptors, including thyroid hormone receptor, and inhibit their ability to transactivate by preventing their binding to their DNA response elements. This gene is included in the surfeit gene cluster, a group of very tightly linked genes that do not share sequence similarity. It is co-transcribed with the U24, U36a, U36b, and U36c small nucleolar RNA genes, which are located in its second, fifth, fourth, and sixth introns, respectively. This gene rearranges with the trk proto-oncogene to form the chimeric oncogene trk-2h, which encodes an oncoprotein consisting of the N terminus of ribosomal protein L7a fused to the receptor tyrosine kinase domain of trk. 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]

RPL7A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.822

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL7A	NM_000972.3	c.688T>A	p.Tyr230Asn	missense_variant	7/8	ENST00000323345.11	NP_000963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL7A	ENST00000323345.11	c.688T>A	p.Tyr230Asn	missense_variant	7/8	1	NM_000972.3	ENSP00000361076.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2024

The c.688T>A (p.Y230N) alteration is located in exon 7 (coding exon 7) of the RPL7A gene. This alteration results from a T to A substitution at nucleotide position 688, causing the tyrosine (Y) at amino acid position 230 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Pathogenic	3.2	M;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-4.7	D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.018	D;D
Sift4G	Uncertain	0.014	D;D
Polyphen		0.96	D;.
Vest4		0.86
MutPred		0.48		Gain of helix (P = 0.0325);.;
MVP		0.71
MPC		1.9
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.16
gMVP		0.99

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-136217918;