NM_004425.4:c.146C>T

Variant names:

• chr1-150509685-C-T
• NM_004425.4:c.146C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004425.4(ECM1):​c.146C>T​(p.Pro49Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P49Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ECM1 NM_004425.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.38

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECM1	NM_004425.4	c.146C>T	p.Pro49Leu	missense_variant	Exon 3 of 10	ENST00000369047.9	NP_004416.2
ECM1	NM_001202858.2	c.146C>T	p.Pro49Leu	missense_variant	Exon 3 of 10		NP_001189787.1
ECM1	NM_022664.3	c.146C>T	p.Pro49Leu	missense_variant	Exon 3 of 9		NP_073155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECM1	ENST00000369047.9	c.146C>T	p.Pro49Leu	missense_variant	Exon 3 of 10	1	NM_004425.4	ENSP00000358043.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.37	.;T;.
Eigen	Benign	0.022
Eigen_PC	Benign	0.014
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	1.8	L;L;L
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-4.8	D;D;D
REVEL	Uncertain	0.34
Sift	Benign	0.052	T;T;T
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.66	P;B;D
Vest4		0.62
MutPred		0.47		Loss of glycosylation at P49 (P = 0.009);Loss of glycosylation at P49 (P = 0.009);Loss of glycosylation at P49 (P = 0.009);
MVP		0.86
MPC		0.21
ClinPred		0.97	D
GERP RS		3.5
Varity_R		0.11
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-150482161;