11-95090157-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015036.3(ENDOD1):​c.230T>G​(p.Val77Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Consequence

ENDOD1
NM_015036.3 missense

Scores

6
10
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.71
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.817

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ENDOD1NM_015036.3 linkuse as main transcriptc.230T>G p.Val77Gly 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.230T>G p.Val77Gly missense_variant 1/21 NM_015036.3 ENSP00000278505 P1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
34

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 GeneticsSep 17, 2021The c.230T>G (p.V77G) alteration is located in exon 1 (coding exon 1) of the ENDOD1 gene. This alteration results from a T to G substitution at nucleotide position 230, causing the valine (V) at amino acid position 77 to be replaced by a glycine (G). 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
Uncertain
0.41
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.16
T
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.39
T
M_CAP
Pathogenic
0.64
D
MetaRNN
Pathogenic
0.82
D
MetaSVM
Uncertain
0.13
D
MutationAssessor
Pathogenic
3.3
M
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.88
D
PROVEAN
Pathogenic
-5.3
D
REVEL
Uncertain
0.57
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0020
D
Polyphen
0.98
D
Vest4
0.58
MutPred
0.59
Gain of disorder (P = 0.0151);
MVP
0.92
MPC
2.4
ClinPred
0.99
D
GERP RS
4.5
Varity_R
0.93
gMVP
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

hg19: chr11-94823321; API