1-150509675-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004425.4(ECM1):​c.136C>T​(p.Pro46Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. P46A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ECM1
NM_004425.4 missense

Scores

8
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.755
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37007117).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ECM1NM_004425.4 linkc.136C>T p.Pro46Ser missense_variant Exon 3 of 10 ENST00000369047.9 NP_004416.2 Q16610-1A0A140VJI7
ECM1NM_001202858.2 linkc.136C>T p.Pro46Ser missense_variant Exon 3 of 10 NP_001189787.1 Q16610-4
ECM1NM_022664.3 linkc.136C>T p.Pro46Ser missense_variant Exon 3 of 9 NP_073155.2 Q16610-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ECM1ENST00000369047.9 linkc.136C>T p.Pro46Ser missense_variant Exon 3 of 10 1 NM_004425.4 ENSP00000358043.4 Q16610-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1455332
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
724340
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:
9.04e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
0.0084
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.43
.;T;.
Eigen
Benign
-0.020
Eigen_PC
Benign
-0.11
FATHMM_MKL
Benign
0.098
N
LIST_S2
Uncertain
0.87
D;D;D
M_CAP
Benign
0.056
D
MetaRNN
Benign
0.37
T;T;T
MetaSVM
Benign
-0.38
T
MutationAssessor
Uncertain
2.1
M;M;M
PrimateAI
Benign
0.33
T
PROVEAN
Uncertain
-4.1
D;D;D
REVEL
Uncertain
0.46
Sift
Uncertain
0.011
D;D;D
Sift4G
Uncertain
0.018
D;D;D
Polyphen
0.99
D;P;P
Vest4
0.37
MutPred
0.67
Loss of catalytic residue at P46 (P = 0.0235);Loss of catalytic residue at P46 (P = 0.0235);Loss of catalytic residue at P46 (P = 0.0235);
MVP
0.91
MPC
0.45
ClinPred
0.97
D
GERP RS
2.3
Varity_R
0.16
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr1-150482151; API