11-95090195-G-T

Variant summary

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

The NM_015036.3(ENDOD1):​c.268G>T​(p.Gly90Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,418,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

ENDOD1
NM_015036.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.650
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]

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=0.15317786).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ENDOD1NM_015036.3 linkuse as main transcriptc.268G>T p.Gly90Cys missense_variant 1/2 ENST00000278505.5 NP_055851.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ENDOD1ENST00000278505.5 linkuse as main transcriptc.268G>T p.Gly90Cys missense_variant 1/21 NM_015036.3 ENSP00000278505 P1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152232
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000254
AC:
2
AN:
78740
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
44288
show subpopulations
Gnomad AFR exome
AF:
0.000833
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:
0.0000375
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000711
AC:
9
AN:
1266128
Hom.:
0
Cov.:
30
AF XY:
0.00000811
AC XY:
5
AN XY:
616640
show subpopulations
Gnomad4 AFR exome
AF:
0.000345
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152232
Hom.:
0
Cov.:
34
AF XY:
0.0000269
AC XY:
2
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000285
Hom.:
0
Bravo
AF:
0.000140
ESP6500AA
AF:
0.00101
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000123
AC:
1

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 submitterclinical testingAmbry GeneticsOct 12, 2021The c.268G>T (p.G90C) 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 268, causing the glycine (G) at amino acid position 90 to be replaced by a cysteine (C). 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
0.23
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0082
T
Eigen
Benign
-0.40
Eigen_PC
Benign
-0.64
FATHMM_MKL
Benign
0.092
N
LIST_S2
Benign
0.32
T
M_CAP
Uncertain
0.23
D
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-0.80
T
MutationAssessor
Benign
1.2
L
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-2.0
N
REVEL
Benign
0.17
Sift
Benign
0.040
D
Sift4G
Uncertain
0.015
D
Polyphen
0.98
D
Vest4
0.17
MVP
0.69
MPC
2.0
ClinPred
0.069
T
GERP RS
-0.13
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.0
Varity_R
0.15
gMVP
0.57

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.

Other links and lift over

dbSNP: rs367564707; hg19: chr11-94823359; API