19-17862107-C-T

Variant names:

• chr19-17862107-C-T
• NM_000980.4:c.212C>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1 BP4 BS2

The NM_000980.4(RPL18A):​c.212C>T​(p.Ser71Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000891 in 1,459,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: RPL18A NM_000980.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.65

Genes affected

RPL18A (HGNC:10311): (ribosomal protein L18a) 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 member of the L18AE family of ribosomal proteins that is a component of the 60S subunit. The encoded protein may play a role in viral replication by interacting with the hepatitis C virus internal ribosome entry site (IRES). This gene is co-transcribed with the U68 snoRNA, located within the third intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity RL18A_HUMAN
• BP4: Computational evidence support a benign effect (MetaRNN=0.36692694).
• BS2: High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL18A	NM_000980.4	c.212C>T	p.Ser71Phe	missense_variant	Exon 3 of 5	ENST00000222247.10	NP_000971.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL18A	ENST00000222247.10	c.212C>T	p.Ser71Phe	missense_variant	Exon 3 of 5	1	NM_000980.4	ENSP00000222247.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000891 AC: 13 AN: 1459570 Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6 AN XY: 726100

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000929

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Benign	0.89
DEOGEN2	Benign	0.24	T;.;.;T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.082
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.73	T;T;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.37	T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.0	L;.;.;.;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.0	D;.;.;.;.
REVEL	Benign	0.21
Sift	Benign	0.46	T;.;.;.;.
Sift4G	Benign	0.34	T;T;T;T;T
Polyphen		0.0020	B;.;.;.;.
Vest4		0.61
MutPred		0.46		Gain of methylation at K70 (P = 0.0359);Gain of methylation at K70 (P = 0.0359);.;.;.;
MVP		0.20
MPC		0.96
ClinPred		0.59	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.43

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: chr19-17972916; COSMIC: COSV99714452; COSMIC: COSV99714452;