Variant 12-47716336-C-G 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_001172439.2(ENDOU):c.715G>C(p.Val239Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000706 in 1,614,094 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 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

ENDOU
NM_001172439.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.979

Variant links:

Genes affected

ENDOU (HGNC:14369): (endonuclease, poly(U) specific) This gene encodes a protein with endoribonuclease activity that binds polyuridine-enriched single-stranded RNA. This gene was initially characterized based on its high expression in placenta but was mischaracterized as a serine protease. In mouse, this gene promotes tolerance to self-antigens by regulating B cell activation-induced cell death (AICD). The protein may be useful as a tumor marker. Multiple alternatively spliced transcript variants encoding distinct protein isoforms have been found for this gene. [provided by RefSeq, Jul 2020]

ENDOU links:

RPAP3-DT (HGNC:55477): (RPAP3 divergent transcript)

RPAP3-DT 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=0.022475839).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ENDOU	NM_001172439.2 linkuse as main transcript	c.715G>C	p.Val239Leu	missense_variant	6/10	ENST00000422538.8
RPAP3-DT	NR_183480.1 linkuse as main transcript	n.77-2811C>G		intron_variant, non_coding_transcript_variant
ENDOU	NM_006025.4 linkuse as main transcript	c.592G>C	p.Val198Leu	missense_variant	5/9
ENDOU	NM_001172440.2 linkuse as main transcript	c.526G>C	p.Val176Leu	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENDOU	ENST00000422538.8 linkuse as main transcript	c.715G>C	p.Val239Leu	missense_variant	6/10	1	NM_001172439.2	P1	P21128-1
RPAP3-DT	ENST00000547799.5 linkuse as main transcript	n.80-1156C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000328

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000107

AC:

AN:

251358

Hom.:

AF XY:

0.0000883

AC XY:

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.0000438

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00182

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000328

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000393

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

AC:

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

Nov 16, 2021

The c.715G>C (p.V239L) alteration is located in exon 6 (coding exon 6) of the ENDOU gene. This alteration results from a G to C substitution at nucleotide position 715, causing the valine (V) at amino acid position 239 to be replaced by a leucine (L). 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

0.31

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.094

.;T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.85

D;T;D

M_CAP

Benign

0.0048

MetaRNN

Benign

0.022

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

2.0

.;M;.

MutationTaster

Benign

0.89

N;N;N;N

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.094

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.031

B;B;B

Vest4

0.24

MVP

0.048

MPC

0.16

ClinPred

0.039

GERP RS

3.8

Varity_R

0.14

gMVP

0.57

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