Variant 11-95090060-G-T 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_015036.3(ENDOD1):c.133G>T(p.Ala45Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,450,530 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: 34)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ENDOD1
NM_015036.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

Variant links:

Genes affected

ENDOD1 (HGNC:29129): (endonuclease domain containing 1) Predicted to enable endonuclease activity; metal ion binding activity; and nucleic acid binding activity. Predicted to be involved in nucleic acid phosphodiester bond hydrolysis. Located in extracellular exosome and membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENDOD1 links:

Genome browser will be placed here

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=0.08457002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENDOD1	NM_015036.3 linkuse as main transcript	c.133G>T	p.Ala45Ser	missense_variant	1/2	ENST00000278505.5	NP_055851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENDOD1	ENST00000278505.5 linkuse as main transcript	c.133G>T	p.Ala45Ser	missense_variant	1/2	1	NM_015036.3	ENSP00000278505	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000448

AC:

AN:

223414

Hom.:

AF XY:

0.00

AC XY:

AN XY:

123066

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000414

AC:

AN:

1450530

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721074

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:

0.00000361

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Oct 05, 2023

The c.133G>T (p.A45S) alteration is located in exon 1 (coding exon 1) of the ENDOD1 gene. This alteration results from a G to T substitution at nucleotide position 133, causing the alanine (A) at amino acid position 45 to be replaced by a serine (S). 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

0.087

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.59

DEOGEN2

Benign

0.0067

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.56

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.085

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.20

REVEL

Benign

0.033

Sift

Benign

0.67

Sift4G

Benign

0.70

Polyphen

0.23

Vest4

0.13

MutPred

0.32

Gain of glycosylation at A45 (P = 0.0034);

MVP

0.46

MPC

1.0

ClinPred

0.043

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.034

gMVP

0.42

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

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