NM_032048.3:c.437A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032048.3(EMILIN2):​c.437A>G​(p.Asn146Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

EMILIN2
NM_032048.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.199
Variant links:
Genes affected
EMILIN2 (HGNC:19881): (elastin microfibril interfacer 2) Predicted to enable extracellular matrix constituent conferring elasticity. Predicted to be involved in cell adhesion. Located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]
LPIN2 (HGNC:14450): (lipin 2) Mouse studies suggest that this gene functions during normal adipose tissue development and may play a role in human triglyceride metabolism. This gene represents a candidate gene for human lipodystrophy, characterized by loss of body fat, fatty liver, hypertriglyceridemia, and insulin resistance. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.058998346).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EMILIN2NM_032048.3 linkc.437A>G p.Asn146Ser missense_variant Exon 4 of 8 ENST00000254528.4 NP_114437.2 Q9BXX0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EMILIN2ENST00000254528.4 linkc.437A>G p.Asn146Ser missense_variant Exon 4 of 8 1 NM_032048.3 ENSP00000254528.3 Q9BXX0
LPIN2ENST00000697039.1 linkc.2547-5130T>C intron_variant Intron 19 of 19 ENSP00000513061.1 A0A8V8TLW1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 01, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.437A>G (p.N146S) alteration is located in exon 4 (coding exon 4) of the EMILIN2 gene. This alteration results from a A to G substitution at nucleotide position 437, causing the asparagine (N) at amino acid position 146 to be replaced by a serine (S). 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
0.066
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
13
DANN
Benign
0.43
DEOGEN2
Benign
0.0026
T
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.58
FATHMM_MKL
Benign
0.67
D
LIST_S2
Benign
0.66
T
M_CAP
Benign
0.0063
T
MetaRNN
Benign
0.059
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.19
N
REVEL
Benign
0.060
Sift
Benign
0.62
T
Sift4G
Benign
0.99
T
Polyphen
0.036
B
Vest4
0.11
MutPred
0.11
Gain of phosphorylation at N146 (P = 0.0075);
MVP
0.25
MPC
0.070
ClinPred
0.067
T
GERP RS
-0.27
Varity_R
0.030
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.16
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: chr18-2890562; API