Variant 4-100447571-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016242.4(EMCN):c.377C>A(p.Thr126Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000922 in 1,593,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

EMCN
NM_016242.4 missense, splice_region

Scores

Splicing: ADA: 0.0004032

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.12

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13981512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMCN	NM_016242.4 linkuse as main transcript	c.377C>A	p.Thr126Asn	missense_variant, splice_region_variant	5/12	ENST00000296420.9	NP_057326.2
LOC124900740	XR_007058203.1 linkuse as main transcript	n.68+26133G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMCN	ENST00000296420.9 linkuse as main transcript	c.377C>A	p.Thr126Asn	missense_variant, splice_region_variant	5/12	1	NM_016242.4	ENSP00000296420	P1	Q9ULC0-1
	ENST00000652064.1 linkuse as main transcript	n.308+25609G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

151872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

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:

0.000235

Gnomad OTH

AF:

0.000961

GnomAD3 exomes

AF:

0.000118

AC:

AN:

246080

Hom.:

AF XY:

0.0000826

AC XY:

AN XY:

133126

show subpopulations

Gnomad AFR exome

AF:

0.0000629

Gnomad AMR exome

AF:

0.000384

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:

0.000126

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000881

AC:

127

AN:

1441770

Hom.:

Cov.:

AF XY:

0.0000849

AC XY:

AN XY:

718162

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000340

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:

0.0000976

Gnomad4 OTH exome

AF:

0.0000837

GnomAD4 genome

AF:

0.000132

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000951

Alfa

AF:

0.000181

Hom.:

Bravo

AF:

0.000125

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000906

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

May 23, 2023

The c.377C>A (p.T126N) alteration is located in exon 5 (coding exon 5) of the EMCN gene. This alteration results from a C to A substitution at nucleotide position 377, causing the threonine (T) at amino acid position 126 to be replaced by an asparagine (N). 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

0.10

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0062

T;.;.;.

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.72

T;T;T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.0

L;L;.;.

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.7

N;D;D;D

REVEL

Benign

0.20

Sift

Benign

0.091

T;D;D;D

Sift4G

Benign

0.061

T;T;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.37

MVP

0.23

MPC

0.0096

ClinPred

0.054

GERP RS

3.4

Varity_R

0.096

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00040

dbscSNV1_RF

Benign

0.056

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