rs4855

Positions:

• chr3-40462224-A-G

Variant summary

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

The NM_001034996.3(RPL14):​c.640A>G​(p.Lys214Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPL14 NM_001034996.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.48

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL14	NM_001034996.3	c.640A>G	p.Lys214Glu	missense_variant	6/6	ENST00000396203.7	NP_001030168.1
RPL14	NM_003973.5	c.640A>G	p.Lys214Glu	missense_variant	6/6		NP_003964.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL14	ENST00000396203.7	c.640A>G	p.Lys214Glu	missense_variant	6/6	1	NM_001034996.3	ENSP00000379506.2
RPL14	ENST00000338970.10	c.640A>G	p.Lys214Glu	missense_variant	6/6	1		ENSP00000345156.6
RPL14	ENST00000479563.5	n.650A>G		non_coding_transcript_exon_variant	5/5	1
RPL14	ENST00000416518.1	c.*263A>G		3_prime_UTR_variant	6/6	3		ENSP00000391446.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.052	T;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.74	.;T
M_CAP	Benign	0.085	D
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.74	N;N
REVEL	Benign	0.16
Sift	Benign	0.12	T;T
Sift4G	Benign	0.10	T;T
Polyphen		0.99	D;D
Vest4		0.51
MutPred		0.28		Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);
MVP		0.65
MPC		0.39
ClinPred		0.77	D
GERP RS		4.4
Varity_R		0.16
gMVP		0.091

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs4855; hg19: chr3-40503715;