Variant 10-73146361-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_007265.3(ECD):c.1042G>A(p.Gly348Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000756 in 1,587,596 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000077 ( 1 hom. )

Consequence

ECD
NM_007265.3 missense, splice_region

Scores

Splicing: ADA: 0.9985

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.99

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:

ECD (HGNC:):

ECD links:

Genome browser will be placed here

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, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECD	NM_007265.3 linkuse as main transcript	c.1042G>A	p.Gly348Arg	missense_variant, splice_region_variant	9/14	ENST00000372979.9	NP_009196.1	O95905-1
ECD	NM_001135752.1 linkuse as main transcript	c.1042G>A	p.Gly348Arg	missense_variant, splice_region_variant	9/15		NP_001129224.1	O95905-3
ECD	NM_001135753.1 linkuse as main transcript	c.913G>A	p.Gly305Arg	missense_variant, splice_region_variant	8/13		NP_001129225.1	O95905-2
ECD	NR_024203.1 linkuse as main transcript	n.874G>A		splice_region_variant, non_coding_transcript_exon_variant	7/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECD	ENST00000372979.9 linkuse as main transcript	c.1042G>A	p.Gly348Arg	missense_variant, splice_region_variant	9/14	1	NM_007265.3	ENSP00000362070.4		O95905-1

Frequencies

GnomAD3 genomes

AF:

0.00000664

AC:

AN:

150574

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000765

AC:

AN:

1437022

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

715116

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:

0.00000908

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.00000664

AC:

AN:

150574

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

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 submitter

clinical testing

Ambry Genetics

Jun 26, 2024

The c.1042G>A (p.G348R) alteration is located in exon 9 (coding exon 8) of the ECD gene. This alteration results from a G to A substitution at nucleotide position 1042, causing the glycine (G) at amino acid position 348 to be replaced by an arginine (R). 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

0.32

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.35

T;.;.

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.033

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Benign

-0.74

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-5.7

D;D;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.52

MutPred

0.78

Loss of ubiquitination at K347 (P = 0.031);.;Loss of ubiquitination at K347 (P = 0.031);

MVP

0.65

MPC

0.48

ClinPred

0.99

GERP RS

5.9

Varity_R

0.58

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.91

SpliceAI score (max)

0.49

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.49

Position offset: -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