rs756947915

Variant names:

• chr14-20583955-C-T
• rs756947915
• NM_001394190.1:c.520G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394190.1(RNASE11):​c.520G>A​(p.Val174Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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: 6.8e-7 (0 hom.)
• Consequence: RNASE11 NM_001394190.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0780
• Publications: 0 publications found

Genes affected

RNASE11 (HGNC:19269): (ribonuclease A family member 11 (inactive)) Predicted to enable endonuclease activity and nucleic acid binding activity. Predicted to be involved in nucleic acid phosphodiester bond hydrolysis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000259060 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030717641).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394190.1. 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
	RNASE11	NM_001394190.1	MANE Select	c.520G>A	p.Val174Ile	missense	Exon 3 of 3	NP_001381119.1	Q5GAN5
	RNASE11	NM_001394189.1		c.520G>A	p.Val174Ile	missense	Exon 3 of 3	NP_001381118.1	Q5GAN5
	RNASE11	NM_001394191.1		c.520G>A	p.Val174Ile	missense	Exon 3 of 3	NP_001381120.1	Q8TAA1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASE11	ENST00000557105.7	TSL:3 MANE Select	c.520G>A	p.Val174Ile	missense	Exon 3 of 3	ENSP00000452412.2	Q8TAA1
	RNASE11	ENST00000432835.6	TSL:1	c.520G>A	p.Val174Ile	missense	Exon 3 of 3	ENSP00000395210.2	Q8TAA1
	RNASE11	ENST00000553849.1	TSL:1	c.520G>A	p.Val174Ile	missense	Exon 2 of 2	ENSP00000451318.1	Q8TAA1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251432 AF XY: 0.00

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461870 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33478

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

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	0.099
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.9
DANN	Benign	0.71
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.078
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.026
Sift	Benign	0.63	T
Sift4G	Benign	0.84	T
Polyphen		0.39	B
Vest4		0.051
MutPred		0.27		Gain of catalytic residue at S173 (P = 0.0021)
MVP		0.085
ClinPred		0.056	T
GERP RS		0.15
Varity_R		0.036
gMVP		0.064
Mutation Taster		=99/1	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: rs756947915; hg19: chr14-21052114;