Variant 17-80415223-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173627.5(ENDOV):c.29C>G(p.Pro10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ENDOV
NM_173627.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.452

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09364927).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENDOV	NM_173627.5 linkuse as main transcript	c.29C>G	p.Pro10Arg	missense_variant	1/10	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.29C>G	p.Pro10Arg	missense_variant	1/10	2	NM_173627.5	ENSP00000429190	P1	Q8N8Q3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461016

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726838

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 05, 2023

The c.29C>G (p.P10R) alteration is located in exon 1 (coding exon 1) of the ENDOV gene. This alteration results from a C to G substitution at nucleotide position 29, causing the proline (P) at amino acid position 10 to be replaced by an arginine (R). 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

0.077

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0039

T;.;T;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.81

T;T;T;T

M_CAP

Benign

0.081

MetaRNN

Benign

0.094

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;.;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.73

N;N;N;N

REVEL

Benign

0.0030

Sift

Benign

0.19

T;T;D;T

Sift4G

Benign

0.23

T;T;T;T

Polyphen

0.028

B;P;P;B

Vest4

0.29

MutPred

0.37

Loss of glycosylation at P10 (P = 0.0086);Loss of glycosylation at P10 (P = 0.0086);Loss of glycosylation at P10 (P = 0.0086);Loss of glycosylation at P10 (P = 0.0086);

MVP

0.33

MPC

0.024

ClinPred

0.11

GERP RS

1.7

Varity_R

0.067

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over