Variant 17-80425597-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173627.5(ENDOV):c.691C>T(p.Arg231Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000252 in 1,588,228 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ENDOV
NM_173627.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.53

Variant links:

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]

ENDOV links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENDOV	NM_173627.5 linkuse as main transcript	c.691C>T	p.Arg231Trp	missense_variant	7/10	ENST00000518137.6	NP_775898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENDOV	ENST00000518137.6 linkuse as main transcript	c.691C>T	p.Arg231Trp	missense_variant	7/10	2	NM_173627.5	ENSP00000429190	P1	Q8N8Q3-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000209

AC:

AN:

1435896

Hom.:

Cov.:

AF XY:

0.0000182

AC XY:

AN XY:

712836

show subpopulations

Gnomad4 AFR exome

AF:

0.0000907

Gnomad4 AMR exome

AF:

0.0000705

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000163

Gnomad4 OTH exome

AF:

0.0000840

GnomAD4 genome

AF:

0.0000656

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000285

Hom.:

Bravo

AF:

0.000200

ESP6500AA

AF:

0.000244

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000167

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2022

The c.691C>T (p.R231W) alteration is located in exon 7 (coding exon 7) of the ENDOV gene. This alteration results from a C to T substitution at nucleotide position 691, causing the arginine (R) at amino acid position 231 to be replaced by a tryptophan (W). 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

Pathogenic

0.77

BayesDel_addAF

Benign

-0.0036

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.;.;T;.;.;T;.;.;.;T

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.92

D;D;D;D;.;.;D;D;D;D;D

M_CAP

Benign

0.068

MetaRNN

Uncertain

0.72

D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.80

MutationAssessor

Pathogenic

4.1

H;.;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

0.99

D;D;D;D;D;D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-7.5

D;D;D;.;.;.;.;.;.;.;D

REVEL

Benign

0.28

Sift

Pathogenic

0.0

D;D;D;.;.;.;.;.;.;.;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;.;.;.;.;.;.;.;.

Vest4

0.65

MVP

0.54

MPC

0.034

ClinPred

1.0

GERP RS

2.7

Varity_R

0.78

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over