Genetic Variant RNASE10:p.Arg210Ser (chr14-20511099-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001386206.3(RNASE10):c.628C>A(p.Arg210Ser) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R210C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RNASE10
NM_001386206.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.67

Publications

0 publications found

Variant links:

Genes affected

RNASE10 (HGNC:19275): (ribonuclease A family member 10 (inactive)) Predicted to enable nucleic acid binding activity. Predicted to be involved in several processes, including heterotypic cell-cell adhesion; positive regulation of flagellated sperm motility; and regulation of fertilization. Predicted to act upstream of or within epithelial cell morphogenesis; seminiferous tubule development; and single fertilization. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

RNASE10 links:

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ACMG classification

Classification was made for transcript

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=0.03602621).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386206.3. 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
	RNASE10	NM_001386206.3	MANE Select	c.628C>A	p.Arg210Ser	missense	Exon 2 of 2	NP_001373135.2	Q5GAN6-1
	RNASE10	NM_001012975.3		c.628C>A	p.Arg210Ser	missense	Exon 2 of 2	NP_001012993.1	Q5GAN6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASE10	ENST00000430083.2	TSL:2 MANE Select	c.628C>A	p.Arg210Ser	missense	Exon 2 of 2	ENSP00000392996.2	Q5GAN6-1
	RNASE10	ENST00000328444.6	TSL:6	c.628C>A	p.Arg210Ser	missense	Exon 1 of 1	ENSP00000333358.5	Q5GAN6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1342538

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

654724

African (AFR)

AF:

0.00

AC:

AN:

29790

American (AMR)

AF:

0.00

AC:

AN:

27198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19620

East Asian (EAS)

AF:

0.00

AC:

AN:

37932

South Asian (SAS)

AF:

0.00

AC:

AN:

64982

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48870

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5248

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1053706

Other (OTH)

AF:

0.00

AC:

AN:

55192

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.048

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.0056

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0094

LIST_S2

Benign

0.26

M_CAP

Benign

0.0023

MetaRNN

Benign

0.036

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-1.7

PrimateAI

Benign

0.30

PROVEAN

Benign

0.47

REVEL

Benign

0.077

Sift

Benign

0.13

Sift4G

Benign

0.51

Polyphen

0.0

Vest4

0.070

MutPred

0.42

Loss of methylation at K209 (P = 0.0411)

MVP

0.014

MPC

0.0087

ClinPred

0.081

GERP RS

-5.3

Varity_R

0.073

gMVP

0.46

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over