chr11-95128454-C-A

Variant summary

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

The NM_015036.3(ENDOD1):​c.378C>A​(p.Ser126Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,104 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 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ENDOD1
NM_015036.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78
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=0.1273858).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ENDOD1NM_015036.3 linkuse as main transcriptc.378C>A p.Ser126Arg missense_variant 2/2 ENST00000278505.5 NP_055851.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ENDOD1ENST00000278505.5 linkuse as main transcriptc.378C>A p.Ser126Arg missense_variant 2/21 NM_015036.3 ENSP00000278505 P1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152228
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249506
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135362
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:
0.0000265
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461876
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
727240
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152228
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
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 submitterclinical testingAmbry GeneticsOct 12, 2022The c.378C>A (p.S126R) alteration is located in exon 2 (coding exon 2) of the ENDOD1 gene. This alteration results from a C to A substitution at nucleotide position 378, causing the serine (S) at amino acid position 126 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
0.24
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0055
T
Eigen
Benign
-0.028
Eigen_PC
Benign
0.097
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.74
T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
0.85
N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.063
Sift
Benign
0.030
D
Sift4G
Benign
0.14
T
Polyphen
0.31
B
Vest4
0.12
MutPred
0.38
Gain of solvent accessibility (P = 0.0202);
MVP
0.56
MPC
0.17
ClinPred
0.68
D
GERP RS
4.7
Varity_R
0.19
gMVP
0.49

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: rs965080410; hg19: chr11-94861618; API