19-49497585-G-T

Variant names:

• chr19-49497585-G-T
• rs368681333
• NM_001015.5:c.213G>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP7 BS2

The NM_001015.5(RPS11):​c.213G>T​(p.Arg71Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,613,844 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. Synonymous variant affecting the same amino acid position (i.e. R71R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: RPS11 NM_001015.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899
• Publications: 0 publications found

Genes affected

RPS11 (HGNC:10384): (ribosomal protein S11) 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 member of the S17P family of ribosomal proteins that is a component of the 40S subunit. This gene is co-transcribed with the small nucleolar RNA gene U35B, which is located in the third intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. [provided by RefSeq, Jul 2012]

SNORD35B (HGNC:17365): (small nucleolar RNA, C/D box 35B)

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13695127).
• BP7: Synonymous conserved (PhyloP=-0.899 with no splicing effect.
• BS2: High AC in GnomAd4 at 15 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001015.5. 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
	RPS11	NM_001015.5	MANE Select	c.213G>T	p.Arg71Arg	synonymous	Exon 3 of 5	NP_001006.1	P62280
	SNORD35B	NR_001285.1		n.-134G>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS11	ENST00000270625.7	TSL:1 MANE Select	c.213G>T	p.Arg71Arg	synonymous	Exon 3 of 5	ENSP00000270625.1	P62280
	RPS11	ENST00000599561.1	TSL:5	c.109G>T	p.Asp37Tyr	missense	Exon 3 of 5	ENSP00000471874.1	M0R1H6
	RPS11	ENST00000912774.1		c.213G>T	p.Arg71Arg	synonymous	Exon 3 of 5	ENSP00000582833.1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251482 AF XY: 0.0000368

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: 0.0000703

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000161 AC: 236 AN: 1461670 Hom.: 0 Cov.: 31 AF XY: 0.000149 AC XY: 108 AN XY: 727172

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

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

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.000210 AC: 233 AN: 1111846

Other (OTH) AF: 0.0000497 AC: 3 AN: 60390

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74338

African (AFR) AF: 0.0000241 AC: 1 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.000106

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.73
DEOGEN2	Benign	0.0039	T
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.14	T
PhyloP100		-0.90
Sift4G	Pathogenic	0.0	D
Vest4		0.37
MVP		0.55
GERP RS		-2.8
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Mutation Taster		=284/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs368681333; hg19: chr19-50000842;