rs3737240

Variant names:

• chr1-150510879-C-A
• rs3737240
• NM_004425.4:c.389C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-150510879-C-A
• chr1-150510879-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004425.4(ECM1):​c.389C>A​(p.Thr130Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T130M) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ECM1 NM_004425.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398
• Publications: 51 publications found

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

ENSG00000307101 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02740711).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECM1	NM_004425.4	c.389C>A	p.Thr130Lys	missense_variant	Exon 6 of 10	ENST00000369047.9	NP_004416.2
ECM1	NM_001202858.2	c.470C>A	p.Thr157Lys	missense_variant	Exon 6 of 10		NP_001189787.1
ECM1	NM_022664.3	c.389C>A	p.Thr130Lys	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	c.389C>A	p.Thr130Lys	missense_variant	Exon 6 of 10	1	NM_004425.4	ENSP00000358043.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 23438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.0090
DANN	Benign	0.51
DEOGEN2	Benign	0.053	.;T;.
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.20	T;T;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.027	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	.;N;N
PhyloP100		-0.40
PrimateAI	Benign	0.31	T
PROVEAN	Benign	1.1	N;N;N
REVEL	Benign	0.077
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.083
MutPred		0.32		.;Gain of ubiquitination at T130 (P = 0.0016);Gain of ubiquitination at T130 (P = 0.0016);
MVP		0.48
MPC		0.12
ClinPred		0.058	T
GERP RS		-5.2
Varity_R		0.042
gMVP		0.16
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3737240; hg19: chr1-150483355;