Genetic Variant EMID1:p.Trp7Gly (chr22-29206057-T-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_133455.4(EMID1):c.19T>G(p.Trp7Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000244 in 1,228,992 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

EMID1
NM_133455.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.107

Publications

0 publications found

Variant links:

Genes affected

EMID1 (HGNC:18036): (EMI domain containing 1) Predicted to be located in several cellular components, including Golgi apparatus; endoplasmic reticulum; and extracellular matrix. Predicted to be part of collagen trimer. [provided by Alliance of Genome Resources, Apr 2022]

EMID1 links:

LOC101929638 (HGNC:):

LOC101929638 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMID1	NM_133455.4 link	c.19T>G	p.Trp7Gly	missense_variant	Exon 1 of 15	ENST00000334018.11	NP_597712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMID1	ENST00000334018.11 link	c.19T>G	p.Trp7Gly	missense_variant	Exon 1 of 15	1	NM_133455.4	ENSP00000335481.6

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151792

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000186

AC:

AN:

1077200

Hom.:

Cov.:

AF XY:

0.00000197

AC XY:

AN XY:

508654

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22804

American (AMR)

AF:

0.00

AC:

AN:

8304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14248

East Asian (EAS)

AF:

0.00

AC:

AN:

26430

South Asian (SAS)

AF:

0.000103

AC:

AN:

19466

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21058

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2910

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

918478

Other (OTH)

AF:

0.00

AC:

AN:

43502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151792

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74132

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41394

American (AMR)

AF:

0.00

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10466

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67888

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 20, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.19T>G (p.W7G) alteration is located in exon 1 (coding exon 1) of the EMID1 gene. This alteration results from a T to G substitution at nucleotide position 19, causing the tryptophan (W) at amino acid position 7 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

0.13

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.083

.;T;T;T;T

Eigen

Benign

0.15

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.57

T;T;T;T;T

M_CAP

Pathogenic

0.98

MetaRNN

Uncertain

0.60

D;D;D;D;D

MetaSVM

Uncertain

-0.043

MutationAssessor

Benign

0.34

N;.;.;.;.

PhyloP100

0.11

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.4

N;D;N;N;N

REVEL

Uncertain

0.60

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Benign

0.097

T;T;T;T;T

Polyphen

0.98

D;.;D;D;.

Vest4

0.46

MutPred

0.70

Gain of disorder (P = 0.003);Gain of disorder (P = 0.003);Gain of disorder (P = 0.003);Gain of disorder (P = 0.003);Gain of disorder (P = 0.003);

MVP

0.91

MPC

0.77

ClinPred

0.71

GERP RS

3.7

PromoterAI

-0.011

Neutral

(source)

gMVP

0.21

Mutation Taster

=87/13

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over