17-80423549-C-T

Variant names:

• chr17-80423549-C-T
• NM_173627.5:c.433C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_173627.5(ENDOV):​c.433C>T​(p.Leu145Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ENDOV NM_173627.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.91
• Publications: 0 publications found

Genes affected

ENDOV (HGNC:26640): (endonuclease V) Enables DNA binding activity; endoribonuclease activity, producing 5'-phosphomonoesters; and single-stranded RNA binding activity. Predicted to be involved in DNA repair. Located in cytoplasmic stress granule and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENDOV	NM_173627.5	c.433C>T	p.Leu145Phe	missense_variant	Exon 5 of 10	ENST00000518137.6	NP_775898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENDOV	ENST00000518137.6	c.433C>T	p.Leu145Phe	missense_variant	Exon 5 of 10	2	NM_173627.5	ENSP00000429190.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.433C>T (p.L145F) alteration is located in exon 5 (coding exon 5) of the ENDOV gene. This alteration results from a C to T substitution at nucleotide position 433, causing the leucine (L) at amino acid position 145 to be replaced by a phenylalanine (F). 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	0.31
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T;.;.;T;.;T;.
Eigen	Uncertain	0.19
Eigen_PC	Benign	-0.0069
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.97	D;D;D;D;D;D;D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.53	D;D;D;D;D;D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.7	M;.;.;.;.;.;.
PhyloP100		3.9
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.6	D;D;D;.;.;.;D
REVEL	Benign	0.21
Sift	Uncertain	0.0060	D;D;D;.;.;.;D
Sift4G	Uncertain	0.018	D;D;D;D;D;D;D
Polyphen		1.0	D;D;D;.;.;.;.
Vest4		0.34
MutPred		0.65		Gain of catalytic residue at L145 (P = 0.0229);.;.;.;.;.;.;
MVP		0.40
MPC		0.14
ClinPred		0.96	D
GERP RS		2.5
PromoterAI		0.0021	Neutral
Varity_R		0.83
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: chr17-78397349; COSMIC: COSV60497815; COSMIC: COSV60497815;