12-47718131-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000422538.8(ENDOU):​c.242G>T​(p.Ser81Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000564 in 1,418,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

ENDOU
ENST00000422538.8 missense, splice_region

Scores

1
18
Splicing: ADA: 0.0007298
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.526
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]
RPAP3-DT (HGNC:55477): (RPAP3 divergent transcript)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07751563).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ENDOUNM_001172439.2 linkuse as main transcriptc.242G>T p.Ser81Ile missense_variant, splice_region_variant 3/10 ENST00000422538.8 NP_001165910.1
RPAP3-DTNR_183480.1 linkuse as main transcriptn.77-1016C>A intron_variant, non_coding_transcript_variant
ENDOUNM_006025.4 linkuse as main transcriptc.119G>T p.Ser40Ile missense_variant, splice_region_variant 2/9 NP_006016.1
ENDOUNM_001172440.2 linkuse as main transcriptc.56-476G>T intron_variant NP_001165911.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ENDOUENST00000422538.8 linkuse as main transcriptc.242G>T p.Ser81Ile missense_variant, splice_region_variant 3/101 NM_001172439.2 ENSP00000397679 P1P21128-1
RPAP3-DTENST00000547799.5 linkuse as main transcriptn.224+495C>A intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000564
AC:
8
AN:
1418386
Hom.:
0
Cov.:
31
AF XY:
0.00000570
AC XY:
4
AN XY:
701180
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000735
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000835
AC:
1

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 submitterclinical testingAmbry GeneticsOct 02, 2023The c.242G>T (p.S81I) alteration is located in exon 3 (coding exon 3) of the ENDOU gene. This alteration results from a G to T substitution at nucleotide position 242, causing the serine (S) at amino acid position 81 to be replaced by an isoleucine (I). 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
0.12
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
15
DANN
Benign
0.88
DEOGEN2
Benign
0.022
.;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.083
N
LIST_S2
Benign
0.57
T;T
M_CAP
Benign
0.0068
T
MetaRNN
Benign
0.078
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
2.0
.;M
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.51
N;N
REVEL
Benign
0.013
Sift
Uncertain
0.020
D;T
Sift4G
Benign
0.10
T;T
Polyphen
0.40
B;B
Vest4
0.38
MVP
0.17
MPC
0.18
ClinPred
0.033
T
GERP RS
-1.2
Varity_R
0.055
gMVP
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00073
dbscSNV1_RF
Benign
0.15
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.

Other links and lift over

dbSNP: rs369895555; hg19: chr12-48111914; API