dbSNP rs186967769: EMCN:p.Val243Phe (chr4-100415922-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_016242.4(EMCN):c.727G>T(p.Val243Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000066 in 151,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V243I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EMCN
NM_016242.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.825

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMCN	NM_016242.4 link	c.727G>T	p.Val243Phe	missense_variant	Exon 10 of 12	ENST00000296420.9	NP_057326.2	Q9ULC0-1Q4W5J1
EMCN	NM_001159694.2 link	c.688G>T	p.Val230Phe	missense_variant	Exon 9 of 11		NP_001153166.1	Q9ULC0-3
EMCN	XM_011532024.4 link	c.727G>T	p.Val243Phe	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>T	p.Val243Phe	missense_variant	Exon 10 of 12	1	NM_016242.4	ENSP00000296420.4	Q9ULC0-1
EMCN	ENST00000305864.7 link	c.478G>T	p.Val160Phe	missense_variant	Exon 7 of 9	1		ENSP00000304780.3	Q9ULC0-2
EMCN	ENST00000511970.5 link	c.688G>T	p.Val230Phe	missense_variant	Exon 9 of 11	2		ENSP00000422432.1	Q9ULC0-3
EMCN	ENST00000506300.5 link	c.197-5567G>T		intron_variant	Intron 3 of 4	4		ENSP00000426515.1	H0YAA7

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151466

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000446

AC:

AN:

224288

Hom.:

AF XY:

0.00

AC XY:

AN XY:

121628

show subpopulations

Gnomad AFR exome

AF:

0.0000695

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1433886

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712864

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151466

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73890

show subpopulations

Gnomad4 AFR

AF:

0.0000243

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.36

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.;.

Eigen

Uncertain

0.64

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

D;T;D

M_CAP

Benign

0.014

MetaRNN

Pathogenic

0.83

D;D;D

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.0

L;.;.

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-4.3

D;D;D

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.92

MutPred

0.70

Loss of sheet (P = 0.0817);.;.;

MVP

0.35

MPC

0.054

ClinPred

0.99

GERP RS

5.7

Varity_R

0.78

gMVP

0.82

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over