Genetic Variant EMB:p.Ala10Ser (chr5-50441124-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198449.3(EMB):c.28G>T(p.Ala10Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,509,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

EMB
NM_198449.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.259

Variant links:

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]

EMB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041505158).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMB	NM_198449.3 link	c.28G>T	p.Ala10Ser	missense_variant	Exon 1 of 9	ENST00000303221.10	NP_940851.1	Q6PCB8-1
EMB	XM_011543146.3 link	c.-39+1828G>T		intron_variant	Intron 2 of 9		XP_011541448.1	Q6PCB8-2
EMB	XM_047416702.1 link	c.-39+218G>T		intron_variant	Intron 1 of 8		XP_047272658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EMB	ENST00000303221.10 link	c.28G>T	p.Ala10Ser	missense_variant	Exon 1 of 9	1	NM_198449.3	ENSP00000302289.5	Q6PCB8-1
EMB	ENST00000508934.5 link	c.28G>T	p.Ala10Ser	missense_variant	Exon 1 of 9	5		ENSP00000425215.1	D6RDX7
EMB	ENST00000506190.1 link	n.92+1828G>T		intron_variant	Intron 2 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

AF:

0.0000214

AC:

AN:

1357732

Hom.:

Cov.:

AF XY:

0.0000224

AC XY:

AN XY:

669372

show subpopulations

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:

0.0000272

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

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

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.28G>T (p.A10S) alteration is located in exon 1 (coding exon 1) of the EMB gene. This alteration results from a G to T substitution at nucleotide position 28, causing the alanine (A) at amino acid position 10 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

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.34

DANN

Benign

0.66

DEOGEN2

Benign

0.047

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0048

LIST_S2

Benign

0.33

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.042

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;.

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.090

N;N

REVEL

Benign

0.018

Sift

Benign

0.38

T;T

Sift4G

Benign

0.47

T;T

Polyphen

0.0010

B;B

Vest4

0.067

MutPred

0.17

Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);

MVP

0.35

MPC

0.087

ClinPred

0.044

GERP RS

-1.6

Varity_R

0.062

gMVP

0.43

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over