Variant chr4-100415958-G-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.691C>A(p.Pro231Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000204 in 1,424,298 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

EMCN
NM_016242.4 missense, splice_region

Scores

Splicing: ADA: 0.9924

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.64

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
EMCN	NM_016242.4 linkuse as main transcript	c.691C>A	p.Pro231Thr	missense_variant, splice_region_variant	10/12	ENST00000296420.9	NP_057326.2
EMCN	NM_001159694.2 linkuse as main transcript	c.652C>A	p.Pro218Thr	missense_variant, splice_region_variant	9/11		NP_001153166.1
EMCN	XM_011532024.4 linkuse as main transcript	c.691C>A	p.Pro231Thr	missense_variant, splice_region_variant	10/12		XP_011530326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMCN	ENST00000296420.9 linkuse as main transcript	c.691C>A	p.Pro231Thr	missense_variant, splice_region_variant	10/12	1	NM_016242.4	ENSP00000296420	P1	Q9ULC0-1
EMCN	ENST00000305864.7 linkuse as main transcript	c.442C>A	p.Pro148Thr	missense_variant, splice_region_variant	7/9	1		ENSP00000304780		Q9ULC0-2
EMCN	ENST00000511970.5 linkuse as main transcript	c.652C>A	p.Pro218Thr	missense_variant, splice_region_variant	9/11	2		ENSP00000422432		Q9ULC0-3
EMCN	ENST00000506300.5 linkuse as main transcript	c.197-5603C>A		intron_variant		4		ENSP00000426515

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000907

AC:

AN:

220486

Hom.:

AF XY:

0.0000167

AC XY:

AN XY:

119666

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000192

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000204

AC:

AN:

1424298

Hom.:

Cov.:

AF XY:

0.0000198

AC XY:

AN XY:

708590

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 NFE exome

AF:

0.0000265

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Feb 06, 2023

The c.691C>A (p.P231T) alteration is located in exon 10 (coding exon 10) of the EMCN gene. This alteration results from a C to A substitution at nucleotide position 691, causing the proline (P) at amino acid position 231 to be replaced by a threonine (T). 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

Uncertain

0.42

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

T;.;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.83

T;T;T

M_CAP

Benign

0.0052

MetaRNN

Uncertain

0.63

D;D;D

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.0

L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-4.8

D;D;D

REVEL

Uncertain

0.62

Sift

Uncertain

0.016

D;D;D

Sift4G

Uncertain

0.021

D;T;D

Polyphen

1.0

D;D;.

Vest4

0.62

MutPred

0.68

Gain of phosphorylation at P231 (P = 0.0543);.;.;

MVP

0.19

MPC

0.056

ClinPred

0.93

GERP RS

5.7

Varity_R

0.38

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.86

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