11-95128912-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015036.3(ENDOD1):​c.836T>C​(p.Met279Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ENDOD1
NM_015036.3 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.23
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.41776758).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ENDOD1NM_015036.3 linkuse as main transcriptc.836T>C p.Met279Thr 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.836T>C p.Met279Thr missense_variant 2/21 NM_015036.3 ENSP00000278505 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 03, 2022The c.836T>C (p.M279T) alteration is located in exon 2 (coding exon 2) of the ENDOD1 gene. This alteration results from a T to C substitution at nucleotide position 836, causing the methionine (M) at amino acid position 279 to be replaced by a threonine (T). 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
Pathogenic
0.87
BayesDel_addAF
Uncertain
0.058
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.010
T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.68
T
M_CAP
Benign
0.042
D
MetaRNN
Benign
0.42
T
MetaSVM
Benign
-0.29
T
MutationAssessor
Uncertain
2.9
M
MutationTaster
Benign
0.76
N
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-1.1
N
REVEL
Uncertain
0.30
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.040
D
Polyphen
0.92
P
Vest4
0.50
MutPred
0.33
Gain of methylation at K280 (P = 0.0267);
MVP
0.82
MPC
0.23
ClinPred
0.89
D
GERP RS
5.9
Varity_R
0.16
gMVP
0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-94862076; COSMIC: COSV53589935; API