19-39435624-G-C

Variant names:

• chr19-39435624-G-C
• rs745820621
• NM_001020.6:c.133C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001020.6(RPS16):​c.133C>G​(p.Arg45Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,400 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R45C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RPS16 NM_001020.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.51
• Publications: 0 publications found

Genes affected

RPS16 (HGNC:10396): (ribosomal protein S16) 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 40S subunit. The protein belongs to the S9P 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3506947).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001020.6. 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
	RPS16	NM_001020.6	MANE Select	c.133C>G	p.Arg45Gly	missense	Exon 2 of 5	NP_001011.1	P62249
	RPS16	NM_001363860.2		c.133C>G	p.Arg45Gly	missense	Exon 2 of 4	NP_001350789.1	Q6IPX4
	RPS16	NM_001321111.2		c.99+34C>G		intron	N/A	NP_001308040.1	M0R210

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS16	ENST00000251453.8	TSL:1 MANE Select	c.133C>G	p.Arg45Gly	missense	Exon 2 of 5	ENSP00000251453.2	P62249
	RPS16	ENST00000339471.8	TSL:1	c.133C>G	p.Arg45Gly	missense	Exon 2 of 4	ENSP00000367806.2	Q6IPX4
	RPS16	ENST00000601655.5	TSL:1	c.99+34C>G		intron	N/A	ENSP00000472231.1	M0R210

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461400 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726966

⚠️ 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: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44720

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: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5522

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111974

Other (OTH) AF: 0.00 AC: 0 AN: 60352

⚠️ 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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.5
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.12
Sift	Benign	0.049	D
Sift4G	Benign	0.20	T
Polyphen		0.91	P
Vest4		0.76
MutPred		0.33		Loss of solvent accessibility (P = 0.0807)
MVP		0.47
MPC		1.3
ClinPred		0.93	D
GERP RS		5.1
PromoterAI		0.017	Neutral
Varity_R		0.54
gMVP		0.73
Mutation Taster		=62/38	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs745820621; hg19: chr19-39926264;