15-66501497-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000968.4(RPL4):​c.554C>T​(p.Ala185Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

RPL4
NM_000968.4 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.68
Variant links:
Genes affected
RPL4 (HGNC:10353): (ribosomal protein L4) 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 L4E family of ribosomal proteins. It is located in the cytoplasm. 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPL4NM_000968.4 linkuse as main transcriptc.554C>T p.Ala185Val missense_variant 6/10 ENST00000307961.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPL4ENST00000307961.11 linkuse as main transcriptc.554C>T p.Ala185Val missense_variant 6/101 NM_000968.4 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 14, 2022The c.554C>T (p.A185V) alteration is located in exon 6 (coding exon 6) of the RPL4 gene. This alteration results from a C to T substitution at nucleotide position 554, causing the alanine (A) at amino acid position 185 to be replaced by a valine (V). 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
Pathogenic
0.73
BayesDel_addAF
Uncertain
0.088
D
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
T;T
Eigen
Uncertain
0.26
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.85
D;D
M_CAP
Benign
0.012
T
MetaRNN
Uncertain
0.58
D;D
MetaSVM
Benign
-0.82
T
MutationAssessor
Benign
1.6
L;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-1.2
N;N
REVEL
Uncertain
0.34
Sift
Benign
0.24
T;T
Sift4G
Benign
0.13
T;T
Polyphen
0.63
P;.
Vest4
0.77
MutPred
0.39
Loss of disorder (P = 0.0786);.;
MVP
0.34
MPC
0.29
ClinPred
0.95
D
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.23
gMVP
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr15-66793835; API