Variant chr10-73139444-T-A details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.68

Variant links:

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]

ECD links:

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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
ECD	NM_007265.3 linkuse as main transcript	c.1286A>T	p.Glu429Val	missense_variant	11/14	ENST00000372979.9
ECD	NM_001135752.1 linkuse as main transcript	c.1385A>T	p.Glu462Val	missense_variant	12/15
ECD	NM_001135753.1 linkuse as main transcript	c.1157A>T	p.Glu386Val	missense_variant	10/13
ECD	NR_024203.1 linkuse as main transcript	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 linkuse as main transcript	c.1286A>T	p.Glu429Val	missense_variant	11/14	1	NM_007265.3	P1	O95905-1
ECD	ENST00000430082.6 linkuse as main transcript	c.1385A>T	p.Glu462Val	missense_variant	12/15	1			O95905-3
ECD	ENST00000454759.6 linkuse as main transcript	c.1157A>T	p.Glu386Val	missense_variant	10/13	1			O95905-2
ECD	ENST00000484976.6 linkuse as main transcript	c.*379A>T		3_prime_UTR_variant, NMD_transcript_variant	9/12	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251428

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135884

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727222

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

Cov.:

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 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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

T;.;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.41

T;T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-5.3

D;D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.013

D;D;D

Polyphen

0.99

D;.;.

Vest4

0.34

MutPred

0.45

Loss of methylation at K433 (P = 0.0725);.;.;

MVP

0.67

MPC

0.46

ClinPred

0.99

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.57

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over