NM_001172439.2:c.692T>C

Variant names:

• chr12-47716359-A-G
• NM_001172439.2:c.692T>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001172439.2(ENDOU):​c.692T>C​(p.Leu231Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENDOU NM_001172439.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.61
• Publications: 0 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.971

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.692T>C	p.Leu231Pro	missense	Exon 6 of 10	NP_001165910.1	P21128-1
	ENDOU	NM_006025.4		c.569T>C	p.Leu190Pro	missense	Exon 5 of 9	NP_006016.1	P21128-2
	ENDOU	NM_001172440.2		c.503T>C	p.Leu168Pro	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.692T>C	p.Leu231Pro	missense	Exon 6 of 10	ENSP00000397679.3	P21128-1
	ENDOU	ENST00000229003.7	TSL:1	c.569T>C	p.Leu190Pro	missense	Exon 5 of 9	ENSP00000229003.3	P21128-2
	ENDOU	ENST00000545824.2	TSL:2	c.503T>C	p.Leu168Pro	missense	Exon 4 of 8	ENSP00000445004.2	P21128-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.076	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		8.6
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.84		Gain of loop (P = 3e-04)
MVP		0.60
MPC		0.82
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.96
gMVP		0.95
Mutation Taster		=12/88	disease causing

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

hg19: chr12-48110142;