rs1213399113

Variant names:

• chr4-100423402-T-C
• rs1213399113
• NM_016242.4:c.418A>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.418A>G​(p.Ser140Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: EMCN NM_016242.4 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38

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]

ENSG00000286150 (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=0.072969735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMCN	NM_016242.4	c.418A>G	p.Ser140Gly	missense_variant, splice_region_variant	Exon 6 of 12	ENST00000296420.9	NP_057326.2
EMCN	NM_001159694.2	c.379A>G	p.Ser127Gly	missense_variant, splice_region_variant	Exon 5 of 11		NP_001153166.1
EMCN	XM_011532024.4	c.418A>G	p.Ser140Gly	missense_variant, splice_region_variant	Exon 6 of 12		XP_011530326.1
LOC124900740	XR_007058203.1	n.68+1964T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMCN	ENST00000296420.9	c.418A>G	p.Ser140Gly	missense_variant, splice_region_variant	Exon 6 of 12	1	NM_016242.4	ENSP00000296420.4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

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

GnomAD4 exome Cov.: 28

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74336

Gnomad4 AFR AF: 0.0000482

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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.418A>G (p.S140G) alteration is located in exon 6 (coding exon 6) of the EMCN gene. This alteration results from a A to G substitution at nucleotide position 418, causing the serine (S) at amino acid position 140 to be replaced by a glycine (G). 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	0.086
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.3
DANN	Benign	0.85
DEOGEN2	Benign	0.0066	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.28	T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.073	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.040
Sift	Uncertain	0.021	D;D
Sift4G	Uncertain	0.023	D;T
Polyphen		0.45	B;.
Vest4		0.16
MutPred		0.40		Loss of glycosylation at S140 (P = 0.0127);.;
MVP		0.030
MPC		0.0092
ClinPred		0.12	T
GERP RS		1.1
Varity_R		0.22
gMVP		0.15

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

Other links and lift over

dbSNP: rs1213399113; hg19: chr4-101344559; COSMIC: COSV99598447;