Variant 10-73134809-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007265.3(ECD):c.1709C>T(p.Pro570Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

ECD
NM_007265.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09618968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECD	NM_007265.3 linkuse as main transcript	c.1709C>T	p.Pro570Leu	missense_variant	14/14	ENST00000372979.9	NP_009196.1	O95905-1
ECD	NM_001135752.1 linkuse as main transcript	c.1808C>T	p.Pro603Leu	missense_variant	15/15		NP_001129224.1	O95905-3
ECD	NM_001135753.1 linkuse as main transcript	c.1580C>T	p.Pro527Leu	missense_variant	13/13		NP_001129225.1	O95905-2
ECD	NR_024203.1 linkuse as main transcript	n.1541C>T		non_coding_transcript_exon_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECD	ENST00000372979.9 linkuse as main transcript	c.1709C>T	p.Pro570Leu	missense_variant	14/14	1	NM_007265.3	ENSP00000362070.4		O95905-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250882

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135724

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:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461524

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727044

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:

0.0000126

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

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 25, 2024

The c.1808C>T (p.P603L) alteration is located in exon 15 (coding exon 14) of the ECD gene. This alteration results from a C to T substitution at nucleotide position 1808, causing the proline (P) at amino acid position 603 to be replaced by a leucine (L). 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

0.075

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.097

T;.;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.096

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Benign

0.074

Sift

Benign

0.12

T;T;D

Sift4G

Benign

0.27

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.046

MutPred

0.43

Loss of glycosylation at S572 (P = 0.0735);.;.;

MVP

0.31

MPC

0.082

ClinPred

0.14

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.083

gMVP

0.093

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