chr11-95128927-A-C
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_015036.3(ENDOD1):āc.851A>Cā(p.Glu284Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000105 in 1,614,114 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000046 ( 0 hom., cov: 32)
Exomes š: 0.00011 ( 3 hom. )
Consequence
ENDOD1
NM_015036.3 missense
NM_015036.3 missense
Scores
2
5
12
Clinical Significance
Conservation
PhyloP100: 3.84
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.04916659).
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ENDOD1 | NM_015036.3 | c.851A>C | p.Glu284Ala | missense_variant | 2/2 | ENST00000278505.5 | NP_055851.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ENDOD1 | ENST00000278505.5 | c.851A>C | p.Glu284Ala | missense_variant | 2/2 | 1 | NM_015036.3 | ENSP00000278505 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152138Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000181 AC: 45AN: 249262Hom.: 0 AF XY: 0.000251 AC XY: 34AN XY: 135224
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GnomAD4 exome AF: 0.000112 AC: 163AN: 1461858Hom.: 3 Cov.: 34 AF XY: 0.000151 AC XY: 110AN XY: 727232
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74426
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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 17, 2023 | The c.851A>C (p.E284A) alteration is located in exon 2 (coding exon 2) of the ENDOD1 gene. This alteration results from a A to C substitution at nucleotide position 851, causing the glutamic acid (E) at amino acid position 284 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of ubiquitination at K281 (P = 0.044);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at