Variant chr4-100415943-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016242.4(EMCN):c.706G>A(p.Glu236Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000201 in 1,590,702 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

EMCN
NM_016242.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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 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/exons	MANE	Protein	UniProt
EMCN	NM_016242.4 link	c.706G>A	p.Glu236Lys	missense_variant	10/12	ENST00000296420.9	NP_057326.2	Q9ULC0-1Q4W5J1
EMCN	NM_001159694.2 link	c.667G>A	p.Glu223Lys	missense_variant	9/11		NP_001153166.1	Q9ULC0-3
EMCN	XM_011532024.4 link	c.706G>A	p.Glu236Lys	missense_variant	10/12		XP_011530326.1	Q9ULC0-1Q4W5J1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EMCN	ENST00000296420.9 link	c.706G>A	p.Glu236Lys	missense_variant	10/12	1	NM_016242.4	ENSP00000296420.4	Q9ULC0-1
EMCN	ENST00000305864.7 link	c.457G>A	p.Glu153Lys	missense_variant	7/9	1		ENSP00000304780.3	Q9ULC0-2
EMCN	ENST00000511970.5 link	c.667G>A	p.Glu223Lys	missense_variant	9/11	2		ENSP00000422432.1	Q9ULC0-3
EMCN	ENST00000506300.5 link	c.197-5588G>A		intron_variant		4		ENSP00000426515.1	H0YAA7

Frequencies

GnomAD3 genomes

AF:

0.0000659

AC:

AN:

151734

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000962

GnomAD3 exomes

AF:

0.0000478

AC:

AN:

229954

Hom.:

AF XY:

0.0000321

AC XY:

AN XY:

124556

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000270

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000280

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000153

AC:

AN:

1438850

Hom.:

Cov.:

AF XY:

0.0000126

AC XY:

AN XY:

715594

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000246

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:

0.00000907

Gnomad4 OTH exome

AF:

0.0000336

GnomAD4 genome

AF:

0.0000659

AC:

AN:

151852

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000394

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000951

Bravo

AF:

0.0000567

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2024

The c.706G>A (p.E236K) 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 706, causing the glutamic acid (E) at amino acid position 236 to be replaced by a lysine (K). 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

Pathogenic

0.91

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.;.

Eigen

Uncertain

0.64

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.65

D;D;D

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.0

L;.;.

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0050

D;D;D

Sift4G

Uncertain

0.013

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.79

MutPred

0.72

Gain of ubiquitination at E236 (P = 0.0247);.;.;

MVP

0.22

MPC

0.053

ClinPred

0.75

GERP RS

5.7

Varity_R

0.44

gMVP

0.55

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