Variant 10-73136897-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_007265.3(ECD):c.1511A>C(p.Asp504Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000923 in 1,613,674 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00097 ( 4 hom. )

Consequence

ECD
NM_007265.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.89

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.076455235).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ECD	NM_007265.3 linkuse as main transcript	c.1511A>C	p.Asp504Ala	missense_variant	13/14	ENST00000372979.9
ECD	NM_001135752.1 linkuse as main transcript	c.1610A>C	p.Asp537Ala	missense_variant	14/15
ECD	NM_001135753.1 linkuse as main transcript	c.1382A>C	p.Asp461Ala	missense_variant	12/13
ECD	NR_024203.1 linkuse as main transcript	n.1343A>C		non_coding_transcript_exon_variant	11/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECD	ENST00000372979.9 linkuse as main transcript	c.1511A>C	p.Asp504Ala	missense_variant	13/14	1	NM_007265.3	P1	O95905-1
ECD	ENST00000430082.6 linkuse as main transcript	c.1610A>C	p.Asp537Ala	missense_variant	14/15	1			O95905-3
ECD	ENST00000454759.6 linkuse as main transcript	c.1382A>C	p.Asp461Ala	missense_variant	12/13	1			O95905-2
ECD	ENST00000484976.6 linkuse as main transcript	c.*604A>C		3_prime_UTR_variant, NMD_transcript_variant	11/12	1

Frequencies

GnomAD3 genomes

AF:

0.000507

AC:

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000286

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000926

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000672

AC:

169

AN:

251424

Hom.:

AF XY:

0.000662

AC XY:

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00121

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000967

AC:

1414

AN:

1461558

Hom.:

Cov.:

AF XY:

0.000928

AC XY:

675

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000719

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.00115

Gnomad4 OTH exome

AF:

0.000779

GnomAD4 genome

AF:

0.000500

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000286

Gnomad4 NFE

AF:

0.000927

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000992

Hom.:

Bravo

AF:

0.000544

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000741

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.000652

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

Sep 30, 2021

The c.1610A>C (p.D537A) alteration is located in exon 14 (coding exon 13) of the ECD gene. This alteration results from a A to C substitution at nucleotide position 1610, causing the aspartic acid (D) at amino acid position 537 to be replaced by an alanine (A). 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

0.16

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.85

D;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.076

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-4.9

D;D;D

REVEL

Benign

0.26

Sift

Uncertain

0.015

D;D;D

Sift4G

Benign

0.11

T;T;T

Polyphen

1.0

D;.;.

Vest4

0.48

MVP

0.61

MPC

0.50

ClinPred

0.16

GERP RS

5.5

Varity_R

0.57

gMVP

0.43

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

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