Variant 14-20510479-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001012975.3(RNASE10):c.8T>C(p.Leu3Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000934 in 1,605,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

RNASE10
NM_001012975.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.722

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:

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=0.063167274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASE10	NM_001386206.3 linkuse as main transcript	c.8T>C	p.Leu3Pro	missense_variant	2/2	ENST00000430083.2	NP_001373135.2
RNASE10	NM_001012975.3 linkuse as main transcript	c.8T>C	p.Leu3Pro	missense_variant	2/2		NP_001012993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASE10	ENST00000430083.2 linkuse as main transcript	c.8T>C	p.Leu3Pro	missense_variant	2/2	2	NM_001386206.3	ENSP00000392996	P1	Q5GAN6-1
RNASE10	ENST00000328444.6 linkuse as main transcript	c.8T>C	p.Leu3Pro	missense_variant	1/1			ENSP00000333358	P1	Q5GAN6-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000453

AC:

AN:

243084

Hom.:

AF XY:

0.0000305

AC XY:

AN XY:

131214

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000605

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000963

AC:

AN:

1453682

Hom.:

Cov.:

AF XY:

0.00000692

AC XY:

AN XY:

722672

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000576

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2023

The c.8T>C (p.L3P) alteration is located in exon 1 (coding exon 1) of the RNASE10 gene. This alteration results from a T to C substitution at nucleotide position 8, causing the leucine (L) at amino acid position 3 to be replaced by a proline (P). 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

0.087

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.036

.;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.39

T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.063

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.20

Sift

Uncertain

0.0010

.;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.0050

.;B

Vest4

0.53

MutPred

0.45

.;Loss of stability (P = 0.0086);

MVP

0.16

MPC

0.0088

ClinPred

0.90

GERP RS

-0.81

Varity_R

0.22

gMVP

0.38

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

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