12-47716542-A-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001172439.2(ENDOU):​c.552-43T>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: not found (cov: 32)

Consequence

ENDOU
NM_001172439.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.02

Publications

6 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]
RPAP3-DT (HGNC:55477): (RPAP3 divergent transcript)

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ENDOUNM_001172439.2 linkc.552-43T>G intron_variant Intron 5 of 9 ENST00000422538.8 NP_001165910.1 P21128-1
ENDOUNM_006025.4 linkc.429-43T>G intron_variant Intron 4 of 8 NP_006016.1 P21128-2
ENDOUNM_001172440.2 linkc.363-43T>G intron_variant Intron 3 of 7 NP_001165911.1 P21128-3
RPAP3-DTNR_183480.1 linkn.77-2605A>C intron_variant Intron 1 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENDOUENST00000422538.8 linkc.552-43T>G intron_variant Intron 5 of 9 1 NM_001172439.2 ENSP00000397679.3 P21128-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
26
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
2.3
DANN
Benign
0.33
PhyloP100
1.0
BranchPoint Hunter
0.0

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

Other links and lift over

dbSNP: rs1235153; hg19: chr12-48110325; API