Genetic Variant EMCN:p.Val243Ile (chr4-100415922-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_016242.4(EMCN):c.727G>A(p.Val243Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000202 in 1,585,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

EMCN
NM_016242.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.37

Variant links:

Genes affected

EMCN (HGNC:16041): (endomucin) EMCN is a mucin-like sialoglycoprotein that interferes with the assembly of focal adhesion complexes and inhibits interaction between cells and the extracellular matrix (Kinoshita et al., 2001 [PubMed 11418125]).[supplied by OMIM, Mar 2008]

EMCN links:

Genome browser will be placed here

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=0.033173323).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMCN	NM_016242.4 link	c.727G>A	p.Val243Ile	missense_variant	Exon 10 of 12	ENST00000296420.9	NP_057326.2	Q9ULC0-1Q4W5J1
EMCN	NM_001159694.2 link	c.688G>A	p.Val230Ile	missense_variant	Exon 9 of 11		NP_001153166.1	Q9ULC0-3
EMCN	XM_011532024.4 link	c.727G>A	p.Val243Ile	missense_variant	Exon 10 of 12		XP_011530326.1	Q9ULC0-1Q4W5J1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EMCN	ENST00000296420.9 link	c.727G>A	p.Val243Ile	missense_variant	Exon 10 of 12	1	NM_016242.4	ENSP00000296420.4	Q9ULC0-1
EMCN	ENST00000305864.7 link	c.478G>A	p.Val160Ile	missense_variant	Exon 7 of 9	1		ENSP00000304780.3	Q9ULC0-2
EMCN	ENST00000511970.5 link	c.688G>A	p.Val230Ile	missense_variant	Exon 9 of 11	2		ENSP00000422432.1	Q9ULC0-3
EMCN	ENST00000506300.5 link	c.197-5567G>A		intron_variant	Intron 3 of 4	4		ENSP00000426515.1	H0YAA7

Frequencies

GnomAD3 genomes

AF:

0.000290

AC:

AN:

151466

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000971

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000417

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000961

GnomAD3 exomes

AF:

0.000343

AC:

AN:

224288

Hom.:

AF XY:

0.000304

AC XY:

AN XY:

121628

show subpopulations

Gnomad AFR exome

AF:

0.000139

Gnomad AMR exome

AF:

0.000355

Gnomad ASJ exome

AF:

0.00488

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000286

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000951

Gnomad OTH exome

AF:

0.000187

GnomAD4 exome

AF:

0.000191

AC:

274

AN:

1433880

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

154

AN XY:

712862

show subpopulations

Gnomad4 AFR exome

AF:

0.0000636

Gnomad4 AMR exome

AF:

0.000330

Gnomad4 ASJ exome

AF:

0.00479

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000299

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000690

Gnomad4 OTH exome

AF:

0.000455

GnomAD4 genome

AF:

0.000303

AC:

AN:

151576

Hom.:

Cov.:

AF XY:

0.000257

AC XY:

AN XY:

74012

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000418

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000951

Alfa

AF:

0.000441

Hom.:

Bravo

AF:

0.000238

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000264

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 29, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.727G>A (p.V243I) alteration is located in exon 10 (coding exon 10) of the EMCN gene. This alteration results from a G to A substitution at nucleotide position 727, causing the valine (V) at amino acid position 243 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.072

T;.;.

Eigen

Uncertain

0.64

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

D;T;D

M_CAP

Benign

0.0065

MetaRNN

Benign

0.033

T;T;T

MetaSVM

Benign

-0.43

MutationAssessor

Benign

1.0

L;.;.

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.87

N;N;N

REVEL

Benign

0.22

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;T;D

Polyphen

1.0

D;D;.

Vest4

0.70

MVP

0.21

MPC

0.052

ClinPred

0.076

GERP RS

5.7

Varity_R

0.37

gMVP

0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over