Variant 12-47716419-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001172439.2(ENDOU):c.632G>A(p.Arg211Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000802 in 1,614,120 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 6 hom. )

Consequence

ENDOU
NM_001172439.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.90

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038414001).

BP6

Variant 12-47716419-C-T is Benign according to our data. Variant chr12-47716419-C-T is described in ClinVar as [Benign]. Clinvar id is 787924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ENDOU	NM_001172439.2 linkuse as main transcript	c.632G>A	p.Arg211Gln	missense_variant	6/10	ENST00000422538.8
RPAP3-DT	NR_183480.1 linkuse as main transcript	n.77-2728C>T		intron_variant, non_coding_transcript_variant
ENDOU	NM_006025.4 linkuse as main transcript	c.509G>A	p.Arg170Gln	missense_variant	5/9
ENDOU	NM_001172440.2 linkuse as main transcript	c.443G>A	p.Arg148Gln	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENDOU	ENST00000422538.8 linkuse as main transcript	c.632G>A	p.Arg211Gln	missense_variant	6/10	1	NM_001172439.2	P1	P21128-1
RPAP3-DT	ENST00000547799.5 linkuse as main transcript	n.80-1073C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00390

AC:

594

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00114

AC:

286

AN:

251436

Hom.:

AF XY:

0.000824

AC XY:

112

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.0151

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000480

AC:

701

AN:

1461846

Hom.:

Cov.:

AF XY:

0.000410

AC XY:

298

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0153

Gnomad4 AMR exome

AF:

0.000827

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000683

Gnomad4 OTH exome

AF:

0.000960

GnomAD4 genome

AF:

0.00390

AC:

594

AN:

152274

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

295

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0129

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000871

Hom.:

Bravo

AF:

0.00465

ESP6500AA

AF:

0.0120

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00132

AC:

160

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

.;T;.

Eigen

Benign

0.0062

Eigen_PC

Benign

0.050

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.90

D;D;D

MetaRNN

Benign

0.0038

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

.;M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.091

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.22

T;T;T

Polyphen

0.82

P;P;P

Vest4

0.36

MVP

0.055

MPC

0.28

ClinPred

0.027

GERP RS

4.2

Varity_R

0.11

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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