Genetic Variant RNASE11:p.Asn155Ser (chr14-20584011-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145250.5(RNASE11):c.464A>G(p.Asn155Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.0000027 ( 0 hom. )

Consequence

RNASE11
NM_145250.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0150

Variant links:

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]

RNASE11 links:

ENSG00000259060 (HGNC:):

ENSG00000259060 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029648453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein
RNASE11	NM_001394189.1 link	c.464A>G	p.Asn155Ser	missense_variant	Exon 3 of 3	NP_001381118.1
RNASE11	NM_001394190.1 link	c.464A>G	p.Asn155Ser	missense_variant	Exon 3 of 3	NP_001381119.1
RNASE11	NM_001394191.1 link	c.464A>G	p.Asn155Ser	missense_variant	Exon 3 of 3	NP_001381120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASE11	ENST00000557105.6 link	c.464A>G	p.Asn155Ser	missense_variant	Exon 3 of 3	3		ENSP00000452412.2		G3V5L6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251428

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135884

show subpopulations

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 SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.464A>G (p.N155S) alteration is located in exon 3 (coding exon 1) of the RNASE11 gene. This alteration results from a A to G substitution at nucleotide position 464, causing the asparagine (N) at amino acid position 155 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.66

DANN

Benign

0.82

DEOGEN2

Benign

0.0061

T;T;T;T;T;T;.;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.55

.;.;.;T;.;.;.;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.030

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

L;L;L;L;L;L;.;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.23

N;N;N;.;N;N;N;N;N

REVEL

Benign

0.030

Sift

Benign

0.55

T;T;T;.;T;T;T;T;T

Sift4G

Benign

0.73

T;T;T;T;T;T;.;.;.

Polyphen

0.13

B;B;B;B;B;B;.;.;.

Vest4

0.079

MutPred

0.33

Gain of disorder (P = 0.0499);Gain of disorder (P = 0.0499);Gain of disorder (P = 0.0499);Gain of disorder (P = 0.0499);Gain of disorder (P = 0.0499);Gain of disorder (P = 0.0499);Gain of disorder (P = 0.0499);Gain of disorder (P = 0.0499);Gain of disorder (P = 0.0499);

MVP

0.12

ClinPred

0.041

GERP RS

-2.3

Varity_R

0.017

gMVP

0.12

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over