chr14-20584039-T-C

Variant names:

• chr14-20584039-T-C
• NM_001394190.1:c.436A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394190.1(RNASE11):​c.436A>G​(p.Ser146Gly) 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. 15/22 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)
• Consequence: RNASE11 NM_001394190.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.216
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07939604).

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.436A>G	p.Ser146Gly	missense	Exon 3 of 3	NP_001381119.1	Q5GAN5
	RNASE11	NM_001394189.1		c.436A>G	p.Ser146Gly	missense	Exon 3 of 3	NP_001381118.1	Q5GAN5
	RNASE11	NM_001394191.1		c.436A>G	p.Ser146Gly	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.436A>G	p.Ser146Gly	missense	Exon 3 of 3	ENSP00000452412.2	Q8TAA1
	RNASE11	ENST00000432835.6	TSL:1	c.436A>G	p.Ser146Gly	missense	Exon 3 of 3	ENSP00000395210.2	Q8TAA1
	RNASE11	ENST00000553849.1	TSL:1	c.436A>G	p.Ser146Gly	missense	Exon 2 of 2	ENSP00000451318.1	Q8TAA1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.093
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.0
DANN	Uncertain	0.98
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0098	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.22
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.14
Sift	Benign	0.19	T
Sift4G	Benign	0.14	T
Polyphen		0.011	B
Vest4		0.16
MutPred		0.26		Gain of catalytic residue at Q141 (P = 2e-04)
MVP		0.36
ClinPred		0.13	T
GERP RS		-0.51
Varity_R		0.052
gMVP		0.056
Mutation Taster		=97/3	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

hg19: chr14-21052198;