4-100517893-T-G

Position:

• chr4-100517893-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016242.4(EMCN):​c.22A>C​(p.Ile8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EMCN NM_016242.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.27

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 (HGNC:):

ACMG classification

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=0.2195116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMCN	NM_016242.4	c.22A>C	p.Ile8Leu	missense_variant	1/12	ENST00000296420.9	NP_057326.2
EMCN	NM_001159694.2	c.22A>C	p.Ile8Leu	missense_variant	1/11		NP_001153166.1
EMCN	XM_011532024.4	c.22A>C	p.Ile8Leu	missense_variant	1/12		XP_011530326.1
EMCN	XM_017008290.2	c.22A>C	p.Ile8Leu	missense_variant	1/6		XP_016863779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMCN	ENST00000296420.9	c.22A>C	p.Ile8Leu	missense_variant	1/12	1	NM_016242.4	ENSP00000296420.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2024

The c.22A>C (p.I8L) alteration is located in exon 1 (coding exon 1) of the EMCN gene. This alteration results from a A to C substitution at nucleotide position 22, causing the isoleucine (I) at amino acid position 8 to be replaced by a leucine (L). 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	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.032
DANN	Benign	0.86
DEOGEN2	Benign	0.0073	T;.;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.64	T;T;T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L;L;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.63	N;N;N;N
REVEL	Benign	0.041
Sift	Benign	0.10	T;D;T;T
Sift4G	Benign	0.21	T;T;T;T
Polyphen		0.13	B;B;.;.
Vest4		0.14
MutPred		0.66		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP		0.030
MPC		0.017
ClinPred		0.21	T
GERP RS		-10
Varity_R		0.053
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-101439050;