12-47716542-A-G

Variant names:

• chr12-47716542-A-G
• rs1235153
• NM_001172439.2:c.552-43T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001172439.2(ENDOU):​c.552-43T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.96 in 1,595,668 control chromosomes in the GnomAD database, including 735,476 homozygotes. 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: 𝑓 0.97 (71585 hom., cov: 32)
  • Exomes 𝑓: 0.96 (663891 hom.)
• Consequence: ENDOU NM_001172439.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 6 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENDOU	NM_001172439.2	c.552-43T>C		intron_variant	Intron 5 of 9	ENST00000422538.8	NP_001165910.1
ENDOU	NM_006025.4	c.429-43T>C		intron_variant	Intron 4 of 8		NP_006016.1
ENDOU	NM_001172440.2	c.363-43T>C		intron_variant	Intron 3 of 7		NP_001165911.1
RPAP3-DT	NR_183480.1	n.77-2605A>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENDOU	ENST00000422538.8	c.552-43T>C		intron_variant	Intron 5 of 9	1	NM_001172439.2	ENSP00000397679.3

Frequencies

GnomAD3 genomes AF: 0.969 AC: 147510 AN: 152184 Hom.: 71525 Cov.: 32

Gnomad AFR AF: 0.993

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.954

Gnomad FIN AF: 0.958

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.956

Gnomad OTH AF: 0.967

GnomAD2 exomes AF: 0.964 AC: 232245 AN: 240850 AF XY: 0.962

Gnomad AFR exome AF: 0.993

Gnomad AMR exome AF: 0.982

Gnomad ASJ exome AF: 0.948

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.953

Gnomad NFE exome AF: 0.958

Gnomad OTH exome AF: 0.966

GnomAD4 exome AF: 0.959 AC: 1384197 AN: 1443366 Hom.: 663891 Cov.: 26 AF XY: 0.958 AC XY: 688410 AN XY: 718270

African (AFR) AF: 0.994 AC: 32817 AN: 33018

American (AMR) AF: 0.981 AC: 42943 AN: 43754

Ashkenazi Jewish (ASJ) AF: 0.947 AC: 24549 AN: 25926

East Asian (EAS) AF: 1.00 AC: 39502 AN: 39504

South Asian (SAS) AF: 0.945 AC: 80524 AN: 85250

European-Finnish (FIN) AF: 0.951 AC: 50545 AN: 53128

Middle Eastern (MID) AF: 0.965 AC: 4207 AN: 4358

European-Non Finnish (NFE) AF: 0.957 AC: 1051738 AN: 1098762

Other (OTH) AF: 0.962 AC: 57372 AN: 59666

GnomAD4 genome AF: 0.969 AC: 147629 AN: 152302 Hom.: 71585 Cov.: 32 AF XY: 0.969 AC XY: 72178 AN XY: 74476

African (AFR) AF: 0.993 AC: 41264 AN: 41568

American (AMR) AF: 0.982 AC: 15028 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 3253 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5170 AN: 5172

South Asian (SAS) AF: 0.954 AC: 4604 AN: 4824

European-Finnish (FIN) AF: 0.958 AC: 10165 AN: 10616

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.956 AC: 65045 AN: 68026

Other (OTH) AF: 0.967 AC: 2045 AN: 2114

Alfa AF: 0.960 Hom.: 12841

Bravo AF: 0.973

Asia WGS AF: 0.983 AC: 3418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.25
PhyloP100		1.0
BranchPoint Hunter		0.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1235153; hg19: chr12-48110325;