4-100479950-C-T

Variant names:

• chr4-100479950-C-T
• rs759272822
• NM_016242.4:c.154G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016242.4(EMCN):​c.154G>A​(p.Val52Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000755 in 1,456,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. V52F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: EMCN NM_016242.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 2 publications found

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]

ENSG00000294250 (HGNC:58859):

LOC124900740 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.098382354).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016242.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMCN	NM_016242.4	MANE Select	c.154G>A	p.Val52Ile	missense	Exon 2 of 12	NP_057326.2
	EMCN	NM_001159694.2		c.154G>A	p.Val52Ile	missense	Exon 2 of 11	NP_001153166.1	Q9ULC0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMCN	ENST00000296420.9	TSL:1 MANE Select	c.154G>A	p.Val52Ile	missense	Exon 2 of 12	ENSP00000296420.4	Q9ULC0-1
	EMCN	ENST00000305864.7	TSL:1	c.154G>A	p.Val52Ile	missense	Exon 2 of 9	ENSP00000304780.3	Q9ULC0-2
	EMCN	ENST00000956441.1		c.154G>A	p.Val52Ile	missense	Exon 2 of 13	ENSP00000626500.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000203 AC: 5 AN: 245818 AF XY: 0.0000376

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000448

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000755 AC: 11 AN: 1456670 Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9 AN XY: 724628

African (AFR) AF: 0.00 AC: 0 AN: 33054

American (AMR) AF: 0.00 AC: 0 AN: 43818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26012

East Asian (EAS) AF: 0.00 AC: 0 AN: 39310

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00000811 AC: 9 AN: 1109816

Other (OTH) AF: 0.0000166 AC: 1 AN: 60184

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.1
DANN	Benign	0.93
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.038
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.16
Sift	Benign	0.21	T
Sift4G	Benign	0.43	T
Polyphen		0.69	P
Vest4		0.055
MutPred		0.51		Gain of helix (P = 0.132)
MVP		0.014
MPC		0.036
ClinPred		0.097	T
GERP RS		-3.8
Varity_R		0.013
gMVP		0.14
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs759272822; hg19: chr4-101401107; COSMIC: COSV99597926; COSMIC: COSV99597926;