5-50411242-T-C

Variant names:

• chr5-50411242-T-C
• NM_198449.3:c.338A>G

Variant summary

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

The NM_198449.3(EMB):​c.338A>G​(p.Asn113Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EMB NM_198449.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.184

Genes affected

EMB (HGNC:30465): (embigin) This gene encodes a transmembrane glycoprotein that is a member of the immunoglobulin superfamily. The encoded protein may be involved in cell growth and development by mediating interactions between the cell and extracellular matrix. A pseudogene of this gene is found on chromosome 1. [provided by RefSeq, Jan 2009]

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=0.18749592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMB	NM_198449.3	c.338A>G	p.Asn113Ser	missense_variant	Exon 3 of 9	ENST00000303221.10	NP_940851.1
EMB	XM_011543146.3	c.188A>G	p.Asn63Ser	missense_variant	Exon 4 of 10		XP_011541448.1
EMB	XM_047416702.1	c.188A>G	p.Asn63Ser	missense_variant	Exon 3 of 9		XP_047272658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMB	ENST00000303221.10	c.338A>G	p.Asn113Ser	missense_variant	Exon 3 of 9	1	NM_198449.3	ENSP00000302289.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 01, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.338A>G (p.N113S) alteration is located in exon 3 (coding exon 3) of the EMB gene. This alteration results from a A to G substitution at nucleotide position 338, causing the asparagine (N) at amino acid position 113 to be replaced by a serine (S). 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	0.070
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.5
DANN	Benign	0.20
DEOGEN2	Benign	0.028	T;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.61	N;N
REVEL	Benign	0.0080
Sift	Benign	1.0	T;T
Sift4G	Benign	0.59	T;T
Polyphen		0.0090	B;.
Vest4		0.12
MutPred		0.26		Gain of disorder (P = 0.0876);.;
MVP		0.25
MPC		0.078
ClinPred		0.040	T
GERP RS		-0.0099
Varity_R		0.027
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr5-49707076;