Genetic Variant ENDOU:p.Arg180Gly (chr12-47716903-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001172439.2(ENDOU):c.538C>G(p.Arg180Gly) 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. R180C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ENDOU
NM_001172439.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.31

Publications

2 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12674293).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172439.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENDOU	NM_001172439.2	MANE Select	c.538C>G	p.Arg180Gly	missense	Exon 5 of 10	NP_001165910.1	P21128-1
ENDOU	NM_006025.4		c.415C>G	p.Arg139Gly	missense	Exon 4 of 9	NP_006016.1	P21128-2
ENDOU	NM_001172440.2		c.349C>G	p.Arg117Gly	missense	Exon 3 of 8	NP_001165911.1	P21128-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENDOU	ENST00000422538.8	TSL:1 MANE Select	c.538C>G	p.Arg180Gly	missense	Exon 5 of 10	ENSP00000397679.3	P21128-1
ENDOU	ENST00000229003.7	TSL:1	c.415C>G	p.Arg139Gly	missense	Exon 4 of 9	ENSP00000229003.3	P21128-2
ENDOU	ENST00000545824.2	TSL:2	c.349C>G	p.Arg117Gly	missense	Exon 3 of 8	ENSP00000445004.2	P21128-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251422

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.036

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.81

M_CAP

Benign

0.025

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

1.3

PrimateAI

Benign

0.18

PROVEAN

Benign

-2.2

REVEL

Benign

0.048

Sift

Benign

0.33

Sift4G

Benign

0.35

Polyphen

0.42

Vest4

0.41

MutPred

0.51

Gain of catalytic residue at L185 (P = 8e-04)

MVP

0.12

MPC

0.28

ClinPred

0.13

GERP RS

0.85

Varity_R

0.14

gMVP

0.36

Mutation Taster

=81/19

polymorphism

(source)

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

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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