rs747738184

Variant names:

• chr19-49498018-A-G
• rs747738184
• NM_001015.5:c.325A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-49498018-A-G
• chr19-49498018-A-C
• chr19-49498018-A-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001015.5(RPS11):​c.325A>G​(p.Met109Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,460,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: RPS11 NM_001015.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.61
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14397833).
• BS2: High AC in GnomAdExome4 at 8 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.325A>G	p.Met109Val	missense	Exon 4 of 5	NP_001006.1	P62280
	SNORD35B	NR_001285.1		n.*212A>G		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS11	ENST00000270625.7	TSL:1 MANE Select	c.325A>G	p.Met109Val	missense	Exon 4 of 5	ENSP00000270625.1	P62280
	RPS11	ENST00000596873.1	TSL:2	c.325A>G	p.Met109Val	missense	Exon 4 of 4	ENSP00000470447.1	M0QZC5
	RPS11	ENST00000599561.1	TSL:5	c.221A>G	p.His74Arg	missense	Exon 4 of 5	ENSP00000471874.1	M0R1H6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251412 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 0.00000548 AC: 8 AN: 1460802 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 726722

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44722

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4946

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111984

Other (OTH) AF: 0.00 AC: 0 AN: 60290

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000165 AC: 2

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	Benign	0.22
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Benign	0.95
DEOGEN2	Benign	0.0099	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.045
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.14	T
PhyloP100		4.6
Sift4G	Pathogenic	0.0	D
Vest4		0.40
MVP		0.78
ClinPred		0.21	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
Mutation Taster		=50/50

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: rs747738184; hg19: chr19-50001275;