Variant 4-100475053-T-C 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.244A>G(p.Thr82Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,533,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

EMCN
NM_016242.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.604

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:

LOC124900740 (HGNC:):

LOC124900740 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=0.15151516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMCN	NM_016242.4 linkuse as main transcript	c.244A>G	p.Thr82Ala	missense_variant	3/12	ENST00000296420.9	NP_057326.2
LOC124900740	XR_007058203.1 linkuse as main transcript	n.69-36080T>C		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.244A>G	p.Thr82Ala	missense_variant	3/12	1	NM_016242.4	ENSP00000296420	P1	Q9ULC0-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000687

AC:

AN:

232810

Hom.:

AF XY:

0.0000635

AC XY:

AN XY:

126030

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000591

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000120

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000111

AC:

153

AN:

1381348

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

686346

show subpopulations

Gnomad4 AFR exome

AF:

0.0000630

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:

0.0000194

Gnomad4 NFE exome

AF:

0.000135

Gnomad4 OTH exome

AF:

0.000123

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000577

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

Jun 01, 2023

The c.244A>G (p.T82A) alteration is located in exon 3 (coding exon 3) of the EMCN gene. This alteration results from a A to G substitution at nucleotide position 244, causing the threonine (T) at amino acid position 82 to be replaced by an alanine (A). 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

0.084

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.45

CADD

Benign

8.3

DANN

Benign

0.97

DEOGEN2

Benign

0.0085

T;.;.;.;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.33

T;T;T;T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.15

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;L;.;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.7

N;N;D;N;N

REVEL

Benign

0.073

Sift

Uncertain

0.024

D;D;D;D;D

Sift4G

Benign

0.20

T;T;D;D;T

Polyphen

0.52

P;P;.;.;.

Vest4

0.038

MVP

0.040

MPC

0.047

ClinPred

0.034

GERP RS

0.75

Varity_R

0.070

gMVP

0.30

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

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