NM_004425.4:c.389C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004425.4(ECM1):c.389C>T(p.Thr130Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,613,194 control chromosomes in the GnomAD database, including 117,482 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 8184 hom., cov: 32)

Exomes 𝑓: 0.38 ( 109298 hom. )

Consequence

ECM1
NM_004425.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.398

Publications

51 publications found

Variant links:

Genes affected

ECM1 (HGNC:3153): (extracellular matrix protein 1) This gene encodes a soluble protein that is involved in endochondral bone formation, angiogenesis, and tumor biology. It also interacts with a variety of extracellular and structural proteins, contributing to the maintenance of skin integrity and homeostasis. Mutations in this gene are associated with lipoid proteinosis disorder (also known as hyalinosis cutis et mucosae or Urbach-Wiethe disease) that is characterized by generalized thickening of skin, mucosae and certain viscera. Alternatively spliced transcript variants encoding distinct isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

ECM1 Gene-Disease associations (from GenCC):

lipoid proteinosis
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P, Orphanet

ECM1 links:

ENSG00000307101 (HGNC:):

ENSG00000307101 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.6169114E-4).

BP6

Variant 1-150510879-C-T is Benign according to our data. Variant chr1-150510879-C-T is described in ClinVar as Benign. ClinVar VariationId is 1222321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ECM1	NM_004425.4 link	c.389C>T	p.Thr130Met	missense_variant	Exon 6 of 10	ENST00000369047.9	NP_004416.2
ECM1	NM_001202858.2 link	c.470C>T	p.Thr157Met	missense_variant	Exon 6 of 10		NP_001189787.1
ECM1	NM_022664.3 link	c.389C>T	p.Thr130Met	missense_variant	Exon 6 of 9		NP_073155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECM1	ENST00000369047.9 link	c.389C>T	p.Thr130Met	missense_variant	Exon 6 of 10	1	NM_004425.4	ENSP00000358043.4

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45210

AN:

151988

Hom.:

8176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0890

Gnomad AMI

AF:

0.430

Gnomad AMR

AF:

0.275

Gnomad ASJ

AF:

0.501

Gnomad EAS

AF:

0.245

Gnomad SAS

AF:

0.327

Gnomad FIN

AF:

0.405

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.401

Gnomad OTH

AF:

0.332

GnomAD2 exomes

AF:

0.339

AC:

83714

AN:

246774

AF XY:

0.349

show subpopulations

Gnomad AFR exome

AF:

0.0803

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.495

Gnomad EAS exome

AF:

0.234

Gnomad FIN exome

AF:

0.410

Gnomad NFE exome

AF:

0.401

Gnomad OTH exome

AF:

0.381

GnomAD4 exome

AF:

0.380

AC:

554645

AN:

1461086

Hom.:

109298

Cov.:

AF XY:

0.381

AC XY:

277222

AN XY:

726876

show subpopulations

African (AFR)

AF:

0.0741

AC:

2480

AN:

33470

American (AMR)

AF:

0.222

AC:

9921

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.487

AC:

12714

AN:

26128

East Asian (EAS)

AF:

0.260

AC:

10311

AN:

39698

South Asian (SAS)

AF:

0.339

AC:

29225

AN:

86242

European-Finnish (FIN)

AF:

0.412

AC:

21965

AN:

53288

Middle Eastern (MID)

AF:

0.425

AC:

2449

AN:

5768

European-Non Finnish (NFE)

AF:

0.399

AC:

443148

AN:

1111398

Other (OTH)

AF:

0.372

AC:

22432

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

18724

37448

56171

74895

93619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13390

26780

40170

53560

66950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.297

AC:

45222

AN:

152108

Hom.:

8184

Cov.:

AF XY:

0.297

AC XY:

22104

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0888

AC:

3688

AN:

41522

American (AMR)

AF:

0.275

AC:

4198

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.501

AC:

1739

AN:

3472

East Asian (EAS)

AF:

0.246

AC:

1271

AN:

5172

South Asian (SAS)

AF:

0.328

AC:

1584

AN:

4826

European-Finnish (FIN)

AF:

0.405

AC:

4281

AN:

10568

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.401

AC:

27257

AN:

67964

Other (OTH)

AF:

0.334

AC:

705

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1502

3004

4507

6009

7511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.360

Hom.:

23438

Bravo

AF:

0.278

TwinsUK

AF:

0.403

AC:

1494

ALSPAC

AF:

0.382

AC:

1474

ESP6500AA

AF:

0.0956

AC:

418

ESP6500EA

AF:

0.398

AC:

3405

ExAC

AF:

0.337

AC:

40827

Asia WGS

AF:

0.329

AC:

1142

AN:

3478

EpiCase

AF:

0.403

EpiControl

AF:

0.407

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Lipid proteinosis

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.11

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.0

.;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.23

T;T;T

MetaRNN

Benign

0.00096

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;N

PhyloP100

-0.40

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.38

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.21

T;T;T

Sift4G

Uncertain

0.021

D;D;D

Vest4

0.056

ClinPred

0.016

GERP RS

-5.2

Varity_R

0.012

gMVP

0.22

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over