12-47716419-C-T

Variant names:

• chr12-47716419-C-T
• rs73300693
• NM_001172439.2:c.632G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001172439.2(ENDOU):​c.632G>A​(p.Arg211Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000802 in 1,614,120 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (6 hom.)
• Consequence: ENDOU NM_001172439.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.90
• Publications: 3 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038414001).
• BP6: Variant 12-47716419-C-T is Benign according to our data. Variant chr12-47716419-C-T is described in ClinVar as Benign. ClinVar VariationId is 787924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENDOU	NM_001172439.2	MANE Select	c.632G>A	p.Arg211Gln	missense	Exon 6 of 10	NP_001165910.1	P21128-1
	ENDOU	NM_006025.4		c.509G>A	p.Arg170Gln	missense	Exon 5 of 9	NP_006016.1	P21128-2
	ENDOU	NM_001172440.2		c.443G>A	p.Arg148Gln	missense	Exon 4 of 8	NP_001165911.1	P21128-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENDOU	ENST00000422538.8	TSL:1 MANE Select	c.632G>A	p.Arg211Gln	missense	Exon 6 of 10	ENSP00000397679.3	P21128-1
	ENDOU	ENST00000229003.7	TSL:1	c.509G>A	p.Arg170Gln	missense	Exon 5 of 9	ENSP00000229003.3	P21128-2
	ENDOU	ENST00000545824.2	TSL:2	c.443G>A	p.Arg148Gln	missense	Exon 4 of 8	ENSP00000445004.2	P21128-3

Frequencies

GnomAD3 genomes AF: 0.00390 AC: 594 AN: 152156 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00114 AC: 286 AN: 251436 AF XY: 0.000824

Gnomad AFR exome AF: 0.0151

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000791

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000480 AC: 701 AN: 1461846 Hom.: 6 Cov.: 32 AF XY: 0.000410 AC XY: 298 AN XY: 727222

African (AFR) AF: 0.0153 AC: 513 AN: 33480

American (AMR) AF: 0.000827 AC: 37 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5732

European-Non Finnish (NFE) AF: 0.0000683 AC: 76 AN: 1112008

Other (OTH) AF: 0.000960 AC: 58 AN: 60392

GnomAD4 genome AF: 0.00390 AC: 594 AN: 152274 Hom.: 3 Cov.: 32 AF XY: 0.00396 AC XY: 295 AN XY: 74468

African (AFR) AF: 0.0129 AC: 535 AN: 41526

American (AMR) AF: 0.00307 AC: 47 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68024

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00174 Hom.: 4

Bravo AF: 0.00465

ESP6500AA AF: 0.0120 AC: 53

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00132 AC: 160

Asia WGS AF: 0.00115 AC: 5 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Benign	0.0062
Eigen_PC	Benign	0.050
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.9
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.091
Sift	Benign	0.12	T
Sift4G	Benign	0.22	T
Polyphen		0.82	P
Vest4		0.36
MVP		0.055
MPC		0.28
ClinPred		0.027	T
GERP RS		4.2
Varity_R		0.11
gMVP		0.47
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs73300693; hg19: chr12-48110202; COSMIC: COSV57465697; COSMIC: COSV57465697;