Variant chr12-47716367-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001172439.2(ENDOU):c.684C>T(p.Asp228Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00433 in 1,614,076 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 126 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 125 hom. )

Consequence

ENDOU
NM_001172439.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.66

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 12-47716367-G-A is Benign according to our data. Variant chr12-47716367-G-A is described in ClinVar as [Benign]. Clinvar id is 784236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.66 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENDOU	NM_001172439.2 link	c.684C>T	p.Asp228Asp	synonymous_variant	6/10	ENST00000422538.8	NP_001165910.1	P21128-1
ENDOU	NM_006025.4 link	c.561C>T	p.Asp187Asp	synonymous_variant	5/9		NP_006016.1	P21128-2
ENDOU	NM_001172440.2 link	c.495C>T	p.Asp165Asp	synonymous_variant	4/8		NP_001165911.1	P21128-3
RPAP3-DT	NR_183480.1 link	n.77-2780G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENDOU	ENST00000422538.8 link	c.684C>T	p.Asp228Asp	synonymous_variant	6/10	1	NM_001172439.2	ENSP00000397679.3		P21128-1

Frequencies

GnomAD3 genomes

AF:

0.0224

AC:

3413

AN:

152120

Hom.:

126

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0782

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00733

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00607

AC:

1526

AN:

251428

Hom.:

AF XY:

0.00442

AC XY:

601

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0818

Gnomad AMR exome

AF:

0.00384

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000378

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00245

AC:

3582

AN:

1461838

Hom.:

125

Cov.:

AF XY:

0.00215

AC XY:

1561

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0824

Gnomad4 AMR exome

AF:

0.00425

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000284

Gnomad4 OTH exome

AF:

0.00459

GnomAD4 genome

AF:

0.0224

AC:

3414

AN:

152238

Hom.:

126

Cov.:

AF XY:

0.0218

AC XY:

1626

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0780

Gnomad4 AMR

AF:

0.00732

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000324

Gnomad4 OTH

AF:

0.0165

Alfa

AF:

0.00712

Hom.:

Bravo

AF:

0.0251

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.27

DANN

Benign

0.62

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