19-39435706-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001020.6(RPS16):​c.51G>A​(p.Lys17Lys) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: RPS16 NM_001020.6 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=2.42 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 6 AD gene.

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>A	p.Lys17Lys	splice_region synonymous	Exon 2 of 5	NP_001011.1	P62249
	RPS16	NM_001363860.2		c.51G>A	p.Lys17Lys	splice_region synonymous	Exon 2 of 4	NP_001350789.1	Q6IPX4
	RPS16	NM_001321111.2		c.51G>A	p.Lys17Lys	splice_region synonymous	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>A	p.Lys17Lys	splice_region synonymous	Exon 2 of 5	ENSP00000251453.2	P62249
	RPS16	ENST00000339471.8	TSL:1	c.51G>A	p.Lys17Lys	splice_region synonymous	Exon 2 of 4	ENSP00000367806.2	Q6IPX4
	RPS16	ENST00000601655.5	TSL:1	c.51G>A	p.Lys17Lys	splice_region synonymous	Exon 2 of 5	ENSP00000472231.1	M0R210

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461134 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726888

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

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: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52760

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111930

Other (OTH) AF: 0.0000331 AC: 2 AN: 60388

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.3
DANN	Benign	0.79
PhyloP100		2.4
PromoterAI		0.022	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;