19-49497585-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001015.5(RPS11):​c.213G>C​(p.Arg71Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPS11 NM_001015.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14826572).
• BP6: Variant 19-49497585-G-C is Benign according to our data. Variant chr19-49497585-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2650248.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.899 with no splicing effect.

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>C	p.Arg71Arg	synonymous	Exon 3 of 5	NP_001006.1	P62280
	SNORD35B	NR_001285.1		n.-134G>C		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>C	p.Arg71Arg	synonymous	Exon 3 of 5	ENSP00000270625.1	P62280
	RPS11	ENST00000599561.1	TSL:5	c.109G>C	p.Asp37His	missense	Exon 3 of 5	ENSP00000471874.1	M0R1H6
	RPS11	ENST00000912774.1		c.213G>C	p.Arg71Arg	synonymous	Exon 3 of 5	ENSP00000582833.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.64
DEOGEN2	Benign	0.0038	T
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.15	T
PhyloP100		-0.90
Sift4G	Pathogenic	0.0	D
Vest4		0.30
MVP		0.58
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)		0.0		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: rs368681333; hg19: chr19-50000842;