19-39435706-C-A

Variant names:

• chr19-39435706-C-A
• rs1344146928
• NM_001020.6:c.51G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001020.6(RPS16):​c.51G>T​(p.Lys17Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPS16 NM_001020.6 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.946

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.51G>T	p.Lys17Asn	missense splice_region	Exon 2 of 5	NP_001011.1	P62249
	RPS16	NM_001363860.2		c.51G>T	p.Lys17Asn	missense splice_region	Exon 2 of 4	NP_001350789.1	Q6IPX4
	RPS16	NM_001321111.2		c.51G>T	p.Lys17Asn	missense splice_region	Exon 2 of 5	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.51G>T	p.Lys17Asn	missense splice_region	Exon 2 of 5	ENSP00000251453.2	P62249
	RPS16	ENST00000339471.8	TSL:1	c.51G>T	p.Lys17Asn	missense splice_region	Exon 2 of 4	ENSP00000367806.2	Q6IPX4
	RPS16	ENST00000601655.5	TSL:1	c.51G>T	p.Lys17Asn	missense splice_region	Exon 2 of 5	ENSP00000472231.1	M0R210

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.41
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.26	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	0.25	D
MutationAssessor	Pathogenic	5.6	H
PhyloP100		2.4
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.95
MutPred		0.79		Loss of methylation at K17 (P = 0.0124)
MVP		0.31
MPC		2.0
ClinPred		1.0	D
GERP RS		0.42
PromoterAI		0.0048	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.90
gMVP		0.99
Mutation Taster		=30/70	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1344146928; hg19: chr19-39926346;