14-20584314-T-C

Variant names:

• chr14-20584314-T-C
• ENST00000432835.6:c.161A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145250.5(RNASE11):​c.161A>G​(p.Asn54Ser) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N54D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNASE11 NM_145250.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10187933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASE11	NM_001394189.1	c.161A>G	p.Asn54Ser	missense_variant	Exon 3 of 3		NP_001381118.1
RNASE11	NM_001394190.1	c.161A>G	p.Asn54Ser	missense_variant	Exon 3 of 3		NP_001381119.1
RNASE11	NM_001394191.1	c.161A>G	p.Asn54Ser	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	c.161A>G	p.Asn54Ser	missense_variant	Exon 3 of 3	3		ENSP00000452412.2
ENSG00000259060	ENST00000555283.1	c.*26A>G		downstream_gene_variant		4		ENSP00000477006.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.161A>G (p.N54S) 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 161, causing the asparagine (N) at amino acid position 54 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	0.17
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.024	T;T;T;T;T;T;.;.;.;.;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.43	.;.;.;T;.;.;.;T;T;T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.10	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;L;L;L;L;L;.;.;.;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.1	N;N;N;.;N;N;N;N;D;D;D
REVEL	Benign	0.017
Sift	Uncertain	0.018	D;D;D;.;D;D;D;D;D;D;D
Sift4G	Uncertain	0.039	D;D;D;D;D;D;.;.;.;.;.
Polyphen		0.35	B;B;B;B;B;B;.;.;.;.;.
Vest4		0.27
MutPred		0.38		Gain of catalytic residue at L52 (P = 0.0054);Gain of catalytic residue at L52 (P = 0.0054);Gain of catalytic residue at L52 (P = 0.0054);Gain of catalytic residue at L52 (P = 0.0054);Gain of catalytic residue at L52 (P = 0.0054);Gain of catalytic residue at L52 (P = 0.0054);Gain of catalytic residue at L52 (P = 0.0054);Gain of catalytic residue at L52 (P = 0.0054);Gain of catalytic residue at L52 (P = 0.0054);Gain of catalytic residue at L52 (P = 0.0054);Gain of catalytic residue at L52 (P = 0.0054);
MVP		0.14
ClinPred		0.19	T
GERP RS		3.0
Varity_R		0.13
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-21052473;