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GeneBe

3-40462212-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001034996.3(RPL14):c.628G>A(p.Ala210Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000046 in 152,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A210E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Consequence

RPL14
NM_001034996.3 missense

Scores

6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.25440988).
BS2
High AC in GnomAd at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPL14NM_001034996.3 linkuse as main transcriptc.628G>A p.Ala210Thr missense_variant 6/6 ENST00000396203.7
RPL14NM_003973.5 linkuse as main transcriptc.628G>A p.Ala210Thr missense_variant 6/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPL14ENST00000396203.7 linkuse as main transcriptc.628G>A p.Ala210Thr missense_variant 6/61 NM_001034996.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152084
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
35
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152084
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74284
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000264

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 GeneticsSep 17, 2021The c.628G>A (p.A210T) alteration is located in exon 6 (coding exon 6) of the RPL14 gene. This alteration results from a G to A substitution at nucleotide position 628, causing the alanine (A) at amino acid position 210 to be replaced by a threonine (T). 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
Benign
0.073
BayesDel_addAF
Uncertain
0.047
T
BayesDel_noAF
Benign
-0.17
Cadd
Benign
20
Dann
Uncertain
0.99
DEOGEN2
Benign
0.056
T;T
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Benign
0.75
D
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.25
T;T
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
0.81
L;L
MutationTaster
Benign
1.0
D;N;N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-0.38
N;N
REVEL
Benign
0.18
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0080
D;D
Polyphen
0.99
D;D
Vest4
0.13
MVP
0.76
MPC
0.27
ClinPred
0.73
D
GERP RS
4.4
Varity_R
0.11
gMVP
0.10

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs945729615; hg19: chr3-40503703; API