chr19-39435885-T-A

Variant names:

• chr19-39435885-T-A
• rs750866168
• NM_001020.6:c.11A>T

Variant summary

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

The NM_001020.6(RPS16):​c.11A>T​(p.Lys4Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,454,072 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. K4R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RPS16 NM_001020.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.78
• 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=0.41211292).

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.11A>T	p.Lys4Met	missense	Exon 1 of 5	NP_001011.1	P62249
	RPS16	NM_001363860.2		c.11A>T	p.Lys4Met	missense	Exon 1 of 4	NP_001350789.1	Q6IPX4
	RPS16	NM_001321111.2		c.11A>T	p.Lys4Met	missense	Exon 1 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.11A>T	p.Lys4Met	missense	Exon 1 of 5	ENSP00000251453.2	P62249
	RPS16	ENST00000339471.8	TSL:1	c.11A>T	p.Lys4Met	missense	Exon 1 of 4	ENSP00000367806.2	Q6IPX4
	RPS16	ENST00000601655.5	TSL:1	c.11A>T	p.Lys4Met	missense	Exon 1 of 5	ENSP00000472231.1	M0R210

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000408 AC: 1 AN: 245204 AF XY: 0.00000751

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454072 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 723816

⚠️ 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: 33476

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111940

Other (OTH) AF: 0.00 AC: 0 AN: 60332

⚠️ 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.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		6.8
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.28		Loss of ubiquitination at K4 (P = 0.0063)
MVP		0.47
MPC		1.9
ClinPred		0.98	D
GERP RS		6.1
PromoterAI		0.064	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.82
gMVP		0.74
Mutation Taster		=28/72	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: rs750866168; hg19: chr19-39926525;