3-40461991-T-G

Position:

• chr3-40461991-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001034996.3(RPL14):​c.407T>G​(p.Leu136Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPL14 NM_001034996.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.48

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13258442).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL14	NM_001034996.3	c.407T>G	p.Leu136Arg	missense_variant	6/6	ENST00000396203.7
RPL14	NM_003973.5	c.407T>G	p.Leu136Arg	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL14	ENST00000396203.7	c.407T>G	p.Leu136Arg	missense_variant	6/6	1	NM_001034996.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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 06, 2023

The c.407T>G (p.L136R) alteration is located in exon 6 (coding exon 6) of the RPL14 gene. This alteration results from a T to G substitution at nucleotide position 407, causing the leucine (L) at amino acid position 136 to be replaced by an arginine (R). 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	0.17
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.025	T;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.48	.;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.28	N;N
REVEL	Benign	0.029
Sift	Benign	0.10	T;T
Sift4G	Benign	0.37	T;T
Polyphen		0.099	B;B
Vest4		0.18
MutPred		0.28		Gain of methylation at L136 (P = 0.0138);Gain of methylation at L136 (P = 0.0138);
MVP		0.27
MPC		0.41
ClinPred		0.46	T
GERP RS		1.4
Varity_R		0.16
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr3-40503482;