17-39201253-C-G

Variant names:

• chr17-39201253-C-G
• rs774934686
• NM_000981.4:c.46C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1 PM2

The NM_000981.4(RPL19):​c.46C>G​(p.Arg16Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,702 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R16C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RPL19 NM_000981.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.83
• Publications: 0 publications found

Genes affected

RPL19 (HGNC:10312): (ribosomal protein L19) 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 L19E family of ribosomal proteins. It is located in the cytoplasm. 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]

ENSG00000299210 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM1: In a modified_residue Citrulline (size 0) in uniprot entity RL19_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000981.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL19	NM_000981.4	MANE Select	c.46C>G	p.Arg16Gly	missense	Exon 2 of 6	NP_000972.1	P84098
	RPL19	NM_001330200.1		c.40C>G	p.Arg14Gly	missense	Exon 2 of 6	NP_001317129.1	J3KTE4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL19	ENST00000225430.9	TSL:1 MANE Select	c.46C>G	p.Arg16Gly	missense	Exon 2 of 6	ENSP00000225430.4	P84098
	RPL19	ENST00000678573.1		c.106C>G	p.Arg36Gly	missense	Exon 1 of 5	ENSP00000503598.1	A0A7I2YQG2
	RPL19	ENST00000869076.1		c.46C>G	p.Arg16Gly	missense	Exon 2 of 6	ENSP00000539135.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461702 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727178

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111856

Other (OTH) AF: 0.00 AC: 0 AN: 60390

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Benign	0.90
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0059	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.070	N
PhyloP100		4.8
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	1.2	N
REVEL	Uncertain	0.38
Sift	Benign	0.78	T
Sift4G	Benign	0.97	T
Polyphen		0.0	B
Vest4		0.76
MutPred		0.45		Loss of MoRF binding (P = 0.0179)
MVP		0.76
MPC		1.3
ClinPred		0.85	D
GERP RS		3.7
Varity_R		0.16
gMVP		0.74
Mutation Taster		=25/75	disease causing

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

Other links and lift over

dbSNP: rs774934686; hg19: chr17-37357506;