3-40457924-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001034996.3(RPL14):​c.38C>G​(p.Ala13Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

RPL14
NM_001034996.3 missense

Scores

8
7
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.31
Variant links:
Genes affected
RPL14 (HGNC:10305): (ribosomal protein L14) 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 L14E family of ribosomal proteins. It contains a basic region-leucine zipper (bZIP)-like domain. The protein is located in the cytoplasm. This gene contains a trinucleotide (GCT) repeat tract whose length is highly polymorphic; these triplet repeats result in a stretch of alanine residues in the encoded protein. Transcript variants utilizing alternative polyA signals and alternative 5'-terminal exons exist but all encode the same protein. 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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.841

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPL14NM_001034996.3 linkuse as main transcriptc.38C>G p.Ala13Gly missense_variant 2/6 ENST00000396203.7
RPL14NM_003973.5 linkuse as main transcriptc.38C>G p.Ala13Gly missense_variant 2/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPL14ENST00000396203.7 linkuse as main transcriptc.38C>G p.Ala13Gly missense_variant 2/61 NM_001034996.3 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
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 GeneticsMar 29, 2022The c.38C>G (p.A13G) alteration is located in exon 2 (coding exon 2) of the RPL14 gene. This alteration results from a C to G substitution at nucleotide position 38, causing the alanine (A) at amino acid position 13 to be replaced by a glycine (G). 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
0.68
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Benign
0.40
T;T;.
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.80
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.70
.;T;T
M_CAP
Benign
0.066
D
MetaRNN
Pathogenic
0.84
D;D;D
MetaSVM
Uncertain
-0.063
T
MutationAssessor
Pathogenic
3.1
M;M;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.79
T
PROVEAN
Uncertain
-3.2
D;D;D
REVEL
Uncertain
0.41
Sift
Uncertain
0.0090
D;D;D
Sift4G
Uncertain
0.021
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.88
MutPred
0.66
Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);
MVP
0.62
MPC
0.97
ClinPred
0.99
D
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.53
gMVP
0.57

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: chr3-40499415; API