10-73139444-T-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_007265.3(ECD):c.1286A>T(p.Glu429Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
ECD
NM_007265.3 missense
NM_007265.3 missense
Scores
2
5
11
Clinical Significance
Conservation
PhyloP100: 6.68
Genes affected
ECD (HGNC:17029): (ecdysoneless cell cycle regulator) Enables histone acetyltransferase binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [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=0.40646103).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ECD | NM_007265.3 | c.1286A>T | p.Glu429Val | missense_variant | 11/14 | ENST00000372979.9 | |
ECD | NM_001135752.1 | c.1385A>T | p.Glu462Val | missense_variant | 12/15 | ||
ECD | NM_001135753.1 | c.1157A>T | p.Glu386Val | missense_variant | 10/13 | ||
ECD | NR_024203.1 | n.1118A>T | non_coding_transcript_exon_variant | 9/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ECD | ENST00000372979.9 | c.1286A>T | p.Glu429Val | missense_variant | 11/14 | 1 | NM_007265.3 | P1 | |
ECD | ENST00000430082.6 | c.1385A>T | p.Glu462Val | missense_variant | 12/15 | 1 | |||
ECD | ENST00000454759.6 | c.1157A>T | p.Glu386Val | missense_variant | 10/13 | 1 | |||
ECD | ENST00000484976.6 | c.*379A>T | 3_prime_UTR_variant, NMD_transcript_variant | 9/12 | 1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251428Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135884
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461846Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727222
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GnomAD4 genome Cov.: 31
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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 22, 2021 | The c.1385A>T (p.E462V) alteration is located in exon 12 (coding exon 11) of the ECD gene. This alteration results from a A to T substitution at nucleotide position 1385, causing the glutamic acid (E) at amino acid position 462 to be replaced by a valine (V). 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
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Loss of methylation at K433 (P = 0.0725);.;.;
MVP
MPC
0.46
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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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